When pain persists - €¦ · • The disc as the most common etiology of chronic low back pain in...
81
When pain persists DISOGENIC LOW BACK PAIN Can we intervene?
Transcript of When pain persists - €¦ · • The disc as the most common etiology of chronic low back pain in...
When pain persists
DISOGENIC LOW BACK PAIN
Can we intervene
The nature of low back pain
bull Elusive diagnosis for specific causative lesion
bull Lends itself to speculation theory patho-anatomical models
bull Discogenic low back pain is a serious medical and social problem and accounts for 26-42 of the patients with chronic low back pain123
bull The prevalence of zygapophysial joints sacroiliac joints and lumbar discs was 31 18 and 42 respectively 1 Facet SI Disc
bull The disc as the most common etiology of chronic low back pain in adults4
References
1 DePalma MJ Ketchum JM Saullo T What is the source of chronic low back pain and does age play a role Pain Med 2011 12 224-233
2 Schwarzer AC Aprill CN Derby R Fortin J Kine G Bogduk N The prevalence and clinical features of internal disc disruption in patients with chronic low back pain Spine (Phila Pa 1976) 1995 20 1878-1883
3 Manchikanti L Singh V Pampati V Damron KS Barnhill RC Beyer C Cash KA Evaluation of the relative contributions of various structures in chronic low back pain Pain Physician 2001 4 308-316
4 Crock HV A reappraisal of intervertebral disc lesions Med J Aust 1970 1 983-989
Irsquom confusedhellip then whyhellip bull Then why does prolotherapy amp our regen med
techniques work on so manyhellip ndash Its about stiffness ndash Stabilization of subtle instabilities ndash A lot of what you are calling SI pain is NOT SI ndash Multiple pain generatorshellip ldquothe breakdownrdquo
bull 5050 7030 6040 8020
ndash The category of discogenic back pain ndash The mechanical behavior and internal disc dynamics
bull Some discogenic syndromes are not amenable to prolotherapy of the posterior elements
Care depends upon the model bull Manual therapist
ndash Manipulation traction massage ndash FOCUS = facet joint sacroiliac joint trigger points etc
bull Physical therapy ndash Exercise conditioning ndash Physical modalities ndash ldquoCORE stabrdquo
bull Physician ndash Muscle relaxants ndash muscle spasm ndash NSAIDs ndash inflammation
bull Pain specialist ndash Narcotics epidural steroids facet joint steroids etc ndash Intra-discal interventions ndash primarily ablative technologies
bull Regen Med ndash Focus on ligaments and connective tissues ndash Slow to recognize the disc as a source of pain
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The nature of low back pain
bull Elusive diagnosis for specific causative lesion
bull Lends itself to speculation theory patho-anatomical models
bull Discogenic low back pain is a serious medical and social problem and accounts for 26-42 of the patients with chronic low back pain123
bull The prevalence of zygapophysial joints sacroiliac joints and lumbar discs was 31 18 and 42 respectively 1 Facet SI Disc
bull The disc as the most common etiology of chronic low back pain in adults4
References
1 DePalma MJ Ketchum JM Saullo T What is the source of chronic low back pain and does age play a role Pain Med 2011 12 224-233
2 Schwarzer AC Aprill CN Derby R Fortin J Kine G Bogduk N The prevalence and clinical features of internal disc disruption in patients with chronic low back pain Spine (Phila Pa 1976) 1995 20 1878-1883
3 Manchikanti L Singh V Pampati V Damron KS Barnhill RC Beyer C Cash KA Evaluation of the relative contributions of various structures in chronic low back pain Pain Physician 2001 4 308-316
4 Crock HV A reappraisal of intervertebral disc lesions Med J Aust 1970 1 983-989
Irsquom confusedhellip then whyhellip bull Then why does prolotherapy amp our regen med
techniques work on so manyhellip ndash Its about stiffness ndash Stabilization of subtle instabilities ndash A lot of what you are calling SI pain is NOT SI ndash Multiple pain generatorshellip ldquothe breakdownrdquo
bull 5050 7030 6040 8020
ndash The category of discogenic back pain ndash The mechanical behavior and internal disc dynamics
bull Some discogenic syndromes are not amenable to prolotherapy of the posterior elements
Care depends upon the model bull Manual therapist
ndash Manipulation traction massage ndash FOCUS = facet joint sacroiliac joint trigger points etc
bull Physical therapy ndash Exercise conditioning ndash Physical modalities ndash ldquoCORE stabrdquo
bull Physician ndash Muscle relaxants ndash muscle spasm ndash NSAIDs ndash inflammation
bull Pain specialist ndash Narcotics epidural steroids facet joint steroids etc ndash Intra-discal interventions ndash primarily ablative technologies
bull Regen Med ndash Focus on ligaments and connective tissues ndash Slow to recognize the disc as a source of pain
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
References
1 DePalma MJ Ketchum JM Saullo T What is the source of chronic low back pain and does age play a role Pain Med 2011 12 224-233
2 Schwarzer AC Aprill CN Derby R Fortin J Kine G Bogduk N The prevalence and clinical features of internal disc disruption in patients with chronic low back pain Spine (Phila Pa 1976) 1995 20 1878-1883
3 Manchikanti L Singh V Pampati V Damron KS Barnhill RC Beyer C Cash KA Evaluation of the relative contributions of various structures in chronic low back pain Pain Physician 2001 4 308-316
4 Crock HV A reappraisal of intervertebral disc lesions Med J Aust 1970 1 983-989
Irsquom confusedhellip then whyhellip bull Then why does prolotherapy amp our regen med
techniques work on so manyhellip ndash Its about stiffness ndash Stabilization of subtle instabilities ndash A lot of what you are calling SI pain is NOT SI ndash Multiple pain generatorshellip ldquothe breakdownrdquo
bull 5050 7030 6040 8020
ndash The category of discogenic back pain ndash The mechanical behavior and internal disc dynamics
bull Some discogenic syndromes are not amenable to prolotherapy of the posterior elements
Care depends upon the model bull Manual therapist
ndash Manipulation traction massage ndash FOCUS = facet joint sacroiliac joint trigger points etc
bull Physical therapy ndash Exercise conditioning ndash Physical modalities ndash ldquoCORE stabrdquo
bull Physician ndash Muscle relaxants ndash muscle spasm ndash NSAIDs ndash inflammation
bull Pain specialist ndash Narcotics epidural steroids facet joint steroids etc ndash Intra-discal interventions ndash primarily ablative technologies
bull Regen Med ndash Focus on ligaments and connective tissues ndash Slow to recognize the disc as a source of pain
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Irsquom confusedhellip then whyhellip bull Then why does prolotherapy amp our regen med
techniques work on so manyhellip ndash Its about stiffness ndash Stabilization of subtle instabilities ndash A lot of what you are calling SI pain is NOT SI ndash Multiple pain generatorshellip ldquothe breakdownrdquo
bull 5050 7030 6040 8020
ndash The category of discogenic back pain ndash The mechanical behavior and internal disc dynamics
bull Some discogenic syndromes are not amenable to prolotherapy of the posterior elements
Care depends upon the model bull Manual therapist
ndash Manipulation traction massage ndash FOCUS = facet joint sacroiliac joint trigger points etc
bull Physical therapy ndash Exercise conditioning ndash Physical modalities ndash ldquoCORE stabrdquo
bull Physician ndash Muscle relaxants ndash muscle spasm ndash NSAIDs ndash inflammation
bull Pain specialist ndash Narcotics epidural steroids facet joint steroids etc ndash Intra-discal interventions ndash primarily ablative technologies
bull Regen Med ndash Focus on ligaments and connective tissues ndash Slow to recognize the disc as a source of pain
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Care depends upon the model bull Manual therapist
ndash Manipulation traction massage ndash FOCUS = facet joint sacroiliac joint trigger points etc
bull Physical therapy ndash Exercise conditioning ndash Physical modalities ndash ldquoCORE stabrdquo
bull Physician ndash Muscle relaxants ndash muscle spasm ndash NSAIDs ndash inflammation
bull Pain specialist ndash Narcotics epidural steroids facet joint steroids etc ndash Intra-discal interventions ndash primarily ablative technologies
bull Regen Med ndash Focus on ligaments and connective tissues ndash Slow to recognize the disc as a source of pain
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Finding the nociceptive pain foci can the average clinician accomplish this
bull How often is an MRI diagnostic
bull In the absence of disc herniation and neurologic deficit comprehensive physical assessment diagnostic technology (MRI EMG etc) identifies cause of low back pain ______ of the time
Manchikenti L Singa V Pampati V et al Evaluation of the relative
contributions of various structures in chronic low back pain Pain Phys 2000
4308-16
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
How can use short this out bull X-rays
bull EMGNCV
bull CT scans
bull MRI
bull SNRB ESI
bull Facet amp SI blocks
bull Pain mapping with local anesthetics
bull Ultrasound
bull Exam
bull Loading
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
2 types of discogenic back pain etiologieshellip
bull Discogenic back pain classified in two types In our a previous study according to discography we classified discogenic low back pain into two types1
ndash Internal annular disruption IAD
ndash Internal endplate disruption (IED)
1 Peng BG Pang XD Li DM Zhang XY Kuang ZD Du MK Gao CH Typing of discogenic
low back pain Zhonghua Guke Zazhi 2009 31 801-805
2 Bogduk N Innervation of the lumbar spine Spine 8(3) 1983
End-plate is innervated by divisions of the
gray rami of the sympathetics and
sinuvertebral nerve2
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The endplate bull Endplate ndash cartilaginous and bony transition
bull Insertion of annular fibers into the end plate cartilage at the inner annulus junction
bull Vascular sinusoids in the marrow space adjacent to the end plate
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The endplate defects A End plate cartilage avulsion resulting from bending motion that causes traction
at the interface between the end plate and inner annulus
B Traumatic node with end plate fragment resulting from excessive compression with a healthy gel-like nucleus pulposus
C Central end plate fracture with exposed trabeculae resulting from excessive compression with a degenerate fibrous nucleus pulposus
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Endplate innervation
bull End plate subchondral bone is innervated by basivertebral nerve the fibers of which reach the bone marrow along with nutrient arteries that enter the vertebra through the posterior basivertebral foramen
bull End plate innervation is comparable to that of the peripheral annulus
bull Nerve density increases at locations of endplate damage
bull Orange dots demo protein gene product 95 (PGP95) positive nerve fibers across endplate
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc Innervation bull DDD increased nerve fibers in the disc
bull Nociceptive nerve fibers grow into what are usually aneural inner parts of the annulus and even into the nucleus 4-5
bull In addition to the sensory nerve fibers there is growing evidence that sympathetic afferents are also increased in degenerated disc and that they play a significant role in low back pain 4-5
bull In human normal disc protein gene product 95-positive nerve fibers innervate the outer layers of the annulus6
bull These nerve fibers are also positive for acetylcholinesterasem NFP SP CGRP VIP neuropeptide Y C-flanking peptide and synaptophysin
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc herniation
bull Mechanical stimuli which are normally innocuous to disc nociceptors can in certain circumstances generate an amplified response which has been termed lsquoperipheral sensitizationrsquo
bull This may explain why some degenerative discs are painful and others not
bull There is growing evidence that these pain receptors in painful disc are peripherally sensitized by the activity of sympathetic efferents which may initiate a pain impulse in response to ischaemia pressure changes or inflammatory irritation7
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
References disc innervation 1 The pathogenesis of discogenic low back painPeng B Wu W Hou S Li P Zhang C Yang Y J Bone
Joint Surg Br 2005 Jan 87(1)62-7
2 Nerve ingrowth into diseased intervertebral disc in chronic back painFreemont AJ Peacock TE Goupille P Hoyland JA OBrien J Jayson MI Lancet 1997 Jul 19 350(9072)178-81
3 Innervation of annulus fibrosis in low back painCoppes MH Marani E Thomeer RT Oudega M Groen GJ Lancet 1990 Jul 21 336(8708)189-90
4 Sensory innervation to the anterior portion of lumbar intervertebral disc Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Spine (Phila Pa 1976) 1996 Aug 15 21(16)1848-51
5 Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H J Bone Joint Surg Br 1998 Jul 80(4)737-42
6 J C Lotz1 A J Fields1 and E C Liebenberg1 The Role of the Vertebral End Plate in Low Back Pain Global Spine J 2013 Jun 3(3) 153ndash164
7 The nerve supply of the lumbar intervertebral disc Edgar MA J Bone Joint Surg Br 2007 Sep 89(9)1135-9
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Innervation
bull Disc innervated segmentally
bull Ventral portions of lower lumbar discs are innervated by upper (L1-L2) dorsal root ganglion
bull Posterior lateral portion from L3-L6 DRG 1-2
bull Nerve fibers reach the lumbar disc through the sinuvertebral nerves or from branches of the paravertebral sympathetic trunks 3
bull Clinical studies have indicated those local anaesthetic blocks of L2 nerve root can relief discogenic low back pain4
ndash Pulsed radiofrequency to L2 DRGhellip
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
references
1 Morinaga T Takahashi K Yamagata M Chiba T Tanaka K Takahashi Y Nakamura S Suseki K Moriya H Sensory innervation to the anterior portion of lumbar intervertebral disc Spine (Phila Pa 1976) 1996211848ndash1851
2 Nakamura S Takahashi K Takahashi Y Morinaga T Shimada Y Moriya H Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats Spine (Phila Pa 1976) 199621917ndash924
3 Suseki K Takahashi Y Takahashi K Chiba T Yamagata M Moriya H Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes A possible pathway for discogenic low back pain J Bone Joint Surg Br 199880737ndash742
4 Nakamura SI Takahashi K Takahashi Y Yamagata M Moriya H The afferent pathways of discogenic low-back pain Evaluation of L2 spinal nerve infiltration J Bone Joint Surg Br 199678606ndash612
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc Innervation bull In the early 1980s Bogduk1 clarified the innervation of the outer
layers of the annulus
ndash The posterior part of the human disc was supplied not only from the sinuvertebral nerve but also received direct branches in its posterolateral aspect from the ramus communicans or the ventral ramus
ndash Branches from the grey ramus communicans also supplied the lateral aspect of the disc
ndash Anterior discal nerves were observed to arise solely from the sympathetic plexus surrounding the anterior longitudinal ligament
1 Bogduk N The innervation of the lumbar spine Spine (Phila Pa 1976)
19838286ndash293
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Neural relationships about the disc
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The disc and endplate
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The disc and endplate
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Michael Modic MD
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Predicting discogenic pain on MRI using Modic criteria
bull Type I
ndash low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with fatty bone marrow
bull Type II
ndash high signal intensity with both images
bull Type III low signal intensity with both images When two types were present on both sides of the intervertebral space only one diagnosis was applied first priority type I second priority type II last priority type III
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI
Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type I changes
ndash Decreased signal intensity onT1 weighted spin echo images and increased signal intensity on T2 weighted images
ndash Disruption and fissuring of the endplates and visualized fibrous tissue
ndash Endplate disruption
ndash Type 1 can convert to type 2
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type 1 changes involve replacement of normal cellular vertebral body marrow by fibrovascular marrow
bull Type 1 endplate enhance after injection of Gd-DTPA reflecting the vascularity of fibrous marrow
bull Type 1 associated with low signal intensity on T2 (desiccation)
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Categorizing degenerative disc disease assessment of changes in the cable bone marrow with MRI Radiology 1999 January 166 (1 Pt 1) 193-199 Clin Orthop Relat Res 1992 June (279) 68-81
bull Type II changes
ndash Increased signal intensity onT 1 weighted images and isointense or slightly increased signal intensity on T2 weighted images
ndash In golf endplate disruption and yellow marrow replacement in the vertebral body
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Summary of Modic changes
bull MRI endplate changes (Modic amp deRoos)
bull Type I (4) decreased signal on T1 increased signal on T2 vascularized fibrous tissue
bull Type II (16) increased T1 isointense T2 local fatty replacement of marrow
bull Type III decreased T1 decreased T2 advanced sclerosis
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
What causes these endplate changes bull 3 prevailing theories
ndash Mechanical ndash Auto-immune ndash Bacterial
bull MECHANICAL ndash In case of a herniation and severe degeneration the loss of nuclear material may increase the
shear forces on the endplates and micro fractures may occur ndash Hence the Modic type 1 changes might initially reflect bleeding oedema and vascularisation
following trauma or the oedema associated with the repair process after micro fractures within the endplate and the vertebral bone
bull AUTOIMMUNE THEORY ndash O - BROWN ndash toxic nucleus tissue invades the endplate and vertebral bone through fractures in the endplates
and causes an inflammatory response It may not only be nucleus1
ndash Brown Break in continuity of endplate leads to sequestered antigen presented to immune cells leading to autoimmune inflammation
bull Release of metalloproteinases into the intervertebral disc digest nuclear proteins causing rapid IDD
1 Crock HV Internal disc disruption A challenge to disc prolapse fifty years on Spine
198611650ndash3
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
What causes these endplate changes
bull BACTERIAL INFECTION ndash Are bacteria present in or around the disc
ndash Stirling et al who removed nuclear tissue under sterile conditions during surgery for lumbar herniated discs found that 53 of the patients were found to be infected with low virulent anaerobic organisms (Proprionibacterium acnes and Corynebacterium propinquum) as opposed to none of the patients who were operated for other spinal disorders [1]
ndash They therefore hypothesised that patients with sciatica have a breach in the structural integrity of the spinal disc possibly from minor trauma which allows access by low virulent micro organisms [1]
bull Concept Reduce transient Bacteremia VIBRATION TOOTHBRUSH
1 Stirling A Worthington T Rafiq M Lambert PA Elliott TS Association between sciatica and
Propionibacterium acnes Lancet 20013572024ndash5
2 Bhanji S Williams B Sheller B et al Transient bacteremia induced by tooth brushing a
comparison of the Sonicare toothbrush with a conventional toothbrush Pediatr Dent 200224295ndash
9
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Schmorls nodes
bull One type exist prior to skeletal maturity 2nd to cartilage defects that remain after notocold regression and growth plate closure
bull They can occur after skeletal maturity with herniation of NP through the end plate ndash This causes fibrovascular marrow changes
ndash Traumatic etilology
ndash IDD with Schmorlrsquos nodes demonstrate dose response (Amount of nuclear proteins exposure)
ISSLS prize winner Lumbar vertebral endplate lesions associations with disc degeneration and back
pain historyWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1490-6
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
The beginning
Break in continuity of the end plate
Introduction of blood born factors and autoimmune response in the annulus
Degradation of internal disc leading to early fissuring of disc
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Endplate references
bull The human intervertebral disc A micro-angiographical study on its vascular supply at various agesHassler O Acta Orthop Scand 1969 40(6)765-72
bull Studies on structural changes in the lumbar annulus fibrosusHIRSCH C SCHAJOWICZ F Acta Orthop Scand 1952 22(1-4)184-231
bull Vertebral end-plate lesions (Schmorls nodes) in the dorsolumbar spineHilton RC Ball J Benn RT Ann Rheum Dis 1976 Apr 35(2)127-32
bull Relationship of Schmorls nodes to vertebral body endplate fractures and acute endplate disk extrusionsWagner AL Murtagh FR Arrington JA Stallworth D AJNR Am J Neuroradiol 2000 Feb 21(2)276-81
bull Lumbar vertebral endplate lesions prevalence classification and association with ageWang Y Videman T Battieacute MC Spine (Phila Pa 1976) 2012 Aug 1 37(17)1432-9
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
IDD Historical perspectives
bull IDD first described by Crock in 1970 and again in 1986
bull Described disruption of internal disc architecture without signs of dural tension or nerve root compression
bull 1995 Schwarzer April Derby Bogduk calculated the prevalence of IDD to be between 30 to 50 within 95 confidence limit
bull They concluded that neither traditional examination findings nor patientrsquos symptoms could predict whether or not the patient had IDD
bull Validated the importance of discography
Crock HV ldquoReappraisal of the intervertebral disc lesionsrdquo Med jour Austrialia 1970 1983-989
Crock HV Internal disc disruption A challenge to disc prolapse 50 years on Spine 1986 11650-3
Schwarzer AC April CN Derby R Bogduk N Kine G ldquothe prevalence of clinical features of
internal disc disruption in patients with chronic low back painrdquo Spine 1995 20 (17) 1878-88
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Provocation discography bull Subjective component
ndash Is critical to evaluate this step carefully
ndash Non-concordant pain
ndash Concordant pain
ndash And at what pressure
bull Derby amp pressure manomentry
bull Classification of disc lesion and disease
bull The annulogram
bull Holt amp the discogram dark ages
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
A case of discogenic back pain
bull JL is a 33-year-old Caucasian male reached out for a roll of paper towels and felt pop in back Had LBP with radicular left leg pain HNP at L4-L5 disc was noted
bull At the time of the initial MRI and L5-S1 annular fissure was noted but for the most part ignored
bull Transient improvement and then pain returned Pain then worsened
bull Pain switched to right leg Shooting leg pains into both legs lasting 1-2 hours RTO to Surgeon who referred him to Pain Med Specialist Started on opiods
bull Had several years of chronic low back and leg pain and unable to work
bull CO constant pain across the L4-S1 worsens with activity
bull Sense of ldquocrushing sensationrdquo from muscle tension Pain extends to buttock with L5 distribution
bull Updated MRI shown to the right
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
A case of discogenic back pain
bull What is the first question that I want answered
bull He marked relief on REIL
bull What does that mean
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Internal Disc Dynamics A Study of 100 Specimens
Jay Shepperd
C Rand
Hastings England
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
A case of discogenic back pain
So what else do you want to know
- There is also a tear at L5-S1
- Is the L5-S1 tear symptomatic
Disco demonstrated the primary painful
disc was L4-L5
Tx
1 Thermal shrink of annular disruption
and surgical disruption at L4-L5
2 Fill defect with sealant growth factors
and cells L4-L5 and L5-S1
3 Manage post op recovery
OUTCOME
1 Patient back to work laying fiberoptic
cables in homes and offices full time
2 Only rare to occasional mild pain
3 Resolution of leg pain
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
It is NOT what you do at the NP but the AF that counts
bull What are you going to do at the AF tissue to resist intra-disc pressure
bull Derangementhellip
bull Many strategies based on classification system and intradiscal dynamics of a given patient
bull The wrong strategy hellip you can make a patient WORSE
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
What did we learn bull We can use symptomatic response to endrange spinal loading to
determine the presence of discogenic back pain
bull We can utilize endrange spinal loading as a therapeutic movement in some patients Those that do not respond may require intervention
bull We learned that MRI was nondiagnostic of the symptomatic disc despite demonstrating HIZ and L4-L5 and L5-S1
bull Discography or analgesic discography was invaluable in making the diagnosis and planning therapeutic intervention
bull What we did not discuss his we utilize a Stewart Magill PhD based spine stabilization program for postprocedural rehabilitation strategies
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Pain worsens with REIL + dural tension
bull Uncontained HNP
ndash No centralization
ndash REIL worsens leg pain
ndash You can predict the findings on MRI with a 1 min exam
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Strategies must vary based on presenting pathologyhellip
bull How are you going to deal with
the nucleus
bull Shrink back nucleus
bull Remove a portion of the
nucleus
bull Are you going to fill void
bull How are you going to change
the mechanical behvior of the
disc in a given presentation
bull Put a bolus of cells in the disc
and you can increase IVD
pressure and worsen HNP
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
NOTE NO UNIVERSAL PROTOCOL WILL EVER EXIST
You must tailor the treatment to The specific pathological state amp
Clinical presentation
No one tool or protocol fits all problems
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Modified McKenzie Examination
Sorting out complex discogenic back pain cases amp combined
syndromes
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Modified McKenzie
bull The full McKenzie examination involves the exploration of various movement patterns and the symptomatic response to endrange loading to classify and characterize patientrsquos to develop a plan for prescription of movement strategy and exercise
bull Modified McKenzie ndash Modified for the interventional spine practitioner
ndash Utilized in conjunction with history MRI discography and other advanced diagnostic interventions to categorize complex cases typically unresponsive to movement exercise including McKenzie
ndash Provides a means of assisting in the development of categorization system typically unrecognized by most interventional physicians
ndash DEMO
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Letrsquos practice
bull 42-year-old presents with acute low back pain
bull Back pain predominantly in lumbosacral region
bull Patient in the lateral shift antalgic posture Rises out of chair in slow and guarded manner
bull Severe pain with spinal extension and standing
bull Patient tolerates lumbar extension in prone position with REIL x 10 reps relieving lower back pain
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Letrsquos practice bull 50-year-old female presents with chronic low
back pain of seven years duration
bull Back pain occurs over most of lower lumbar spine extends over the posterior buttock and proximal thigh
bull Neurological examination normal
bull Back pain does not improve with REIL RFIL Side glides nor manipulation
bull Marked desiccation and disc space narrowing at L4 L5 and L5-S1
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Letrsquos practice bull 47-year-old male with history of
episodes of back pain generally improved with chiropractic care in the past
bull Patient presents with low back and peripheral leg pain with positive girl tension signs
bull REIL release late pain but does not relieve low back pain
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Letrsquos practice bull 47-year-old with previous history of low
back pain generally relieved with chiropractic manipulation in the past
bull Presents with low back and peripheral leg pain with positive dural tension signs
bull Low back pain and leg pain unrelieved by REIL
bull Peripheral leg pain worsens with REIL
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Letrsquos practice
bull 43-year-old female with history of low back pain in the past generally relieved with chiropractic manipulation
bull Presents with low back pain with some peripheral buttock and thigh pain bilaterally
bull Negative dural tension signs
bull Back pain relieved with REIL but when she stands pain returns within two minutes
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
McKenzie or not to McKenzie
bull McKenzie method is a popular treatment for low back pain among physical therapists
bull Clinical studies have indicated that the McKenzie method is slightly more effective than manipulation or is equal to strengthening training for patients with chronic low back pain1
bull You canrsquot use anything universally
1 Petersen T Larsen K Jacobsen S One-year follow-up comparison of the effectiveness of
McKenzie treatment and strengthening training for patients with chronic low back pain outcome
and prognostic factors Spine (Phila Pa1976) 2007 32 2948-2956
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
McKenzie or not to McKenzie
bull You can and should use McKenzie to help triage classify and categorize your discogenic back pain patient
bull You can determine if there is a directional preferencehellip
bull You can determine if it MIGHT be appropriate to apply McKenzie exercises
bull If you do not know the symptomatic response to loadinghellip then you only know 2 things about your patienthellip
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Modified McKenzie - categorization
bull Examples described here describe simplistic use of this exam technique
bull Time does not permit description of systematically categorizing of multiple pain generators and complex patients
bull Additional techniques described by McGill
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Rehab or Warehab
Movement strategies and
core stabilization techniques
critical to clinical outcomes
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Real core stabhellip
bull Many progressions of exercises to stiffen and balance the anterior chain and posterior chain in a spine sparing manner
bull Concept ndash Stiffen brace and protect a balanced
neutral position
ndash Exploration of postures and movements that are triggers for pain and eliminate them
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Rehab vs Warehab
bull Robin Robinson PT
bull Stuart McGill PhD
ndash Early amhellip No stretching mob repeated flexion
ndash Side plank not cables
ndash Stir the pothellip not crunches
NO
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Provocation Discography amp Analgesic Discography
Understanding the controversy
Overcoming the barriers
Modifying methodology
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Provocation diskography bull Precision injection of contrast into disk nucleus
stimulate nerve endings via 2 mechanisms
ndash Chemical stimulus from contact between contrast in sensitized tissues
ndash Mechanical stimulus resulting from fluid distending stress
bull False positive rate increased with patientrsquos to demonstrate somatizations psychometric testing should be considered and included
OrsquoNeill C Derby R percutaneous diskectomy using nuclear plasty International 21st course
of percutaneous endoscopic spinal surgery and complement are techniques
Zurek Switzerland 2003
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Provocation using pressure manometry bull Total volume injected and should not be gt3-35 cc
ndash Otherwise his increases rate of false positive findings bull Contract should be injected slowly
ndash Only in certain instances should contrast injected quickly (Advanced degenerative disk with leak through endplate or annulus to get to 50 PSI)
bull Higher injection speeds may cause rapid pressure elevations leading to increased pressure differences between nucleus and manometer and between the dynamic and static pressures
bull Typical opening pressures 5-25 PSI ndash Opening pressure gt30 PSI = needle is within annulus
bull Disk slowly pressurized injecting 05 cc increments with syringe attached to pressure manometer
bull Slow injection speed more closely reflects real intradiscal pressures bull Endpoint
ndash Subjective pain = 6 last 10 ndash Intradiscal pressure gt50 PSI above opening pressure with a grade 3 annular tear ndash 80-100 PSI a normal-appearing disk ndash Total of 35 cc contrast
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Discography
bull Is an extension of the clinical examination
bull Requires a careful clinical analysis and clinical correlation
bull The palpation fingerhellip
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Analgesic discography bull More attractive than provocation of discography
bull Personal experiencehellip
bull Derby et al compared 4 different techniques ndash Local alone
ndash Local with contrast
ndash Local after provocation disco
ndash Etc
bull Analgesic discography demonstrated high false-negative rate
bull Fears of provocation discography is high Positive
Derby R Et al Comparison of Four Different Analgesic Discogram Protocols Comparing the
Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful
Lumbar Intervertebral Discs Pain Medicine 2012 13 1547ndash1553
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Intradiscal methylene blue
bull 2010 A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back painPeng B Pang X Wu Y Zhao C Song X Pain 2010 Apr 149(1)124-9
bull Study showed a clinically meaningful pain reduction in 89 of IMBI-treated patients
bull The rationale for this treatment is that methylene blue (MB) is neurolytic
ndash Destroys terminal nerve endings
bull 2011 repeated in the Netherlands ndash 40 responded to the treatment) in a well-selected
group of patients suffering discogenic pain
bull 2015 repeated with RTC underway also in the Netherlands
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
A case of discogenic pain
bull 52 yo female Attorney at law with many years of chronic low back pain
bull Athletic many sports and recreational activities
bull Extreme skiing
bull Partial relief with facet blocks - SI
bull Significant temp relief with
REIL
bull DISCOhellip ndash Which dischellip
L5S1 functional autofusion Positive L4-L5 disc
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Case ldquoMy sacroiliac will not holdrdquo
bull 49-year-old Caucasian male with history of pain over the right sacroiliac joint
bull Pain provocation maneuvers such as
ndash ASLR-SASLR
ndash Ganslens
ndash Yoemans
ndash Lasslet
ndash Shear
ndash Etc
Brown Derby Weins 1992
L4-L5 Discogenic Pain
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Pseudosacroiliac syndrome
bull Mrs K 40 yo with chronic SI pain
ndash OMT DC Rehab
ndash Prolo
ndash MMB
ndash Facet injections
ndash ESI
ndash Acupunture
ndash hellip
DISC
- Which one
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disk histology amp biochemistry
bull Chondrocytes
ndash Predominate
ndash Tolerate an avascular environment
ndash Synthesize matrix in which they are suspended then maintained and repair it
bull Fibrocytes
ndash Primarily in outer annulus
bull Collagen confers tensile strength to disk
bull Proteoglycan
ndash stabilized by Link Proteins (LP 1 LP 2 LP 3)
ndash Versican decorin biglycan fibromodulin lumican
Chondrocytes
Fibrocytes
Liu J Roughley PJ identification of human intravertebral disk
Stromelysin and its involvement in matrix degradationJ Orthop Res 9568-575 1991
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Degenerative Disc Disease
bull Repeated biomechanical forces may lead to the loss of cohesion between bundles of the annulus leading to fissuring
bull These fissures are repaired by ingrowth of granulation tissue which leads to vascularization and thats initiating autoimmune phenomena
bull Fractures of the endplate leading to exposure of sequestered antigen and autoimmune phenomena
Ham Hyun Kim Eung Shick Kang Chang Dong Han Autoimmune responses in the
generated lumbar disc Yonsei Medical Journal Volume 22 No 1 1981
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc degeneration
bull First matrix changes occur in the center nucleus
ndash fragmentation of proteoglycans
ndash decreasing proteoglycan and water concentration
bull Proteoglycan ends in the in plain regulate movement of solutes into and out of the disc Roberts et al 1996
bull Removal of proteoglycan from the endplate accelerates the loss of proteoglycan from the nucleus
bull Atherosclerosis with the lumbar artery = decreased blood flow to endplate also contributes Kauppila et al 1997
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc degeneration
bull Type I collagen = annulus fibrosis
ndash Small amount of II III V VI IX
bull Type II collagen = inner annulus and nucleus pulposus
ndash Small amount of I II VI XI
bull Vertebral endplate
ndash Considered part of the disc
ndash Composed of thin layer of cortical bone covered by hyaline cartilage
ndash produced by typical chondrocytes
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Increase in intradiscal pressure in IDD
bull Pressure build up in the IDD Onik explains that the intervertebral disc may be considered an osmotic system and because of the breakdown in macro molecules during the fourth and fifth decades of life the number of particles in the intervertebral disc increases which in turn causes a concomitant rise in the osmotic pressure secondary to an influx of fluid which in turn increases the intradiscal pressure
bull In order to relieve the pressure annular fissures developed that resultant osmotic annular tears and disc protrusions and pain
Onik G et al ldquoPercutaneous lumbar discectomy using an new aspiration proberdquo AJR 1985 1441137-1140
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Genetics and back pain
bull Genetic variations in the structural componets of the disc
ndash Collagen IX
ndash Aggrecan Ala-Kokko L Genetic risk factors for lumbar
disk diseaseAnn Med 2000 23442-7
bull Collagen IX
ndash Gln326Trp Alpha 2 chain
ndash Arg103Trp Alpha 3 Passilta Pet al first common genetic risk factor
for lumbar disk disease J Am Med Assoc 2001 2851843- 9
bull IL-1 polymorphisms IL-6 TNF
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Disc regenerative injection procedurehellip
Pipedreams or reality in our Future
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Foundation of Regen Med
Prolotherapy
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Stem cell vs engineering bull STEM CELLS
ndash ADSC ndash Autologous BMAC MSC ndash Induced pluripotent SC ndash Endogenous progenitor cells
bull Notochord
ndash NP cells ndash AF cells ndash NCP ndash Umbilical cord stem cells ndash Cultured and expanded
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Autologous BMC IVD injection
bull This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC with durable pain relief (71 VAS reduction) and ODI Oswestry Disability Index improvements (gtthinsp64 ) through two years
Pettine K Suzuki R Sand T et al Treatment of discogenic back pain
with autologous bone marrow concentrate injection with minimum two
year follow-up International Orthopaedics (SICOT) (2016) 40 135
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Hydrogels in IVD DDD bull Certain hydrogels have shown promising results promoting both
the viability of injected cells as well as their differentiation into NP-like cells1
bull Transplantation of MSCs in a hydrogel carrier induced regenerative effects in degenerated IVDs
bull SDF-1 incorporation in proper delivery systems is able to promote cell recruitment to an injury site and increase the potential of tissue regeneration2
bull Combined SDF-1 thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel promote MSC migration to disc
1 Sakai D Mochida J Iwashina T Hiyama A Omi H Imai M et al Regenerative effects of
transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated
intervertebral disc Biomaterials 200627335e45
2 Pereira CL et al The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the
recruitment of MSCs in degenerating intervertebral discs Biomaterials 35 (2014) 8144e8153
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
In search of scaffoldinghellip bull A variety of biomaterials have been used for fabricating scaffolds in NP tissue
engineering 1-7
ndash chitosanhydroxybutyl ndash chitosan alginate ndash collagenatelocollagen ndash gelatin ndash Hyaluronic acid ndash calcium polyphosphate ndash poly-D-L-lactide (PDLA) ndash demineralized bone matrix (DBM) ndash small intestine submucosa (SIS) ndash carboxymethylcellulose ndash PGAndashhyaluronan
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
References
1 OrsquoHalloran DM Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc Tissue Eng 131927ndash 1954
2 Chan SC Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapyndashfeasible or fiction Swiss Med Wkly 142w13598
3 Alini M Roughley PJ Antoniou J Stoll T Aebi M (2002) A biological approach to treating disc degeneration not for today but maybe for tomorrow Eur Spine J 11(Suppl 2)S215ndashS220
4 Nesti LJ Li WJ Shanti RM Jiang YJ Jackson W Freedman BA Kuklo TR Giuliani JR Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam Tissue Eng Part A 141527ndash1537
5 Woiciechowsky C Abbushi A Zenclussen ML Casalis P Kruger JP Freymann U Endres M Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds J Tissue Eng Regen Med
6 Pei M Shoukry M Li J Daffner SD France JC Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration Spine (Phila Pa 1976) 371538ndash1547 Eur Spine J (2013) 221090ndash1100 1097 123
7 Gupta MS Cooper ES Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels potential for nucleus pulposus replacement Tissue Eng Part A 172903ndash2910
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Intradiscal PRP bull 12 good articles 2004-2015 concerning the use of PRP in IDD bull 6 were lsquolsquoin vitrorsquorsquo studies bull 6 were lsquolsquoin vivorsquorsquo studies bull INVITRO
ndash Studied effect on NP and AF cells and proliferation ndash The most frequently analyzed variables were cell proliferation and
extracellular matrix regeneration in terms of different proteoglycan (PG) levelsPG-mRNA expression
bull Only one paper analyzed PL regenerative potential bull All the included studies underlined the positive histological results
demonstrating that PRP induces ECM regeneration and cell proliferation bull Early IDD not late IDD with a dead disc and few cells
Formica et al Eur Spine J (2015) 242377ndash2386
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
How what when
bull How does that alter the mechanical behavior of the disc
bull Which category and type of disc lesion is it best suited for
bull Our results have been inconsistent We are not using intradiscal PRP at this time
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
Stem cell amp tissue engineering for DDD amp discogenic pain
What is the evidencehellip
Our experiencehellip
What we are doinghellip
Research activitieshellip
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
THANK YOU
Michael N Brown MD
1515 116th NE
Bellevue WA 98004
drbr1aolcom
425 326-1665
