1PRESENTED BY :: DR SAURABH SINGHORAL AND MAXILLOFACIAL SURGERY

– BY DR ALBERT SCHWEITZER

History• Latin word ‘poena’ – punishment from God. • Aristotle - first to distinguish 5 physical senses and

considered pain to be the ‘passion of the soul’ • Plato – contented pain and pleasure arose from

within the body.• The Bible – reference to pain not only in relationship

to injury or illness but also anguish of soul.

An unpleasant sensory and emotional experience associated with actual or

potential tissue damage or described in terms of such damage.

- IASPAn unpleasant emotional experience

usually initiated by a noxious stimulus and transmitted over a specialized neural

network to the central nervous system where it is interpreted as such.

- Monheim

Components of pain• Fast pain• Slow pain

FIBRE TYPE

FUNCTION CONDUCTION VELOCITY(minutes / sec)

SPIKE DURATION(milisec)

Myelinated Fibres

Aα Proprioception, somatic motor 30-1200.4-0.5Aβ Touch, pressure and motor

function30-120

Aγ Motor to muscle spindles 15-35Aδ Pain, temperature, touch 5-25

Myelinated fibres

B Preganglionic autonomic fibres 3-15 1.2

Unmyelinated Fibres

sC (dorsal root)

Pain, temperature, touch and conducts impulses generated by cutaneous receptors

0.7-1.3 2

d γ C (sym-pathetic)

Postganglionic sympathetic fibres

0.1-2.0 2

SENSORY COMPONENT MOTOR

COMPONENT

Development of Nociceptors• Develop from neural crest stem cells. • Neural crest cells are responsible mainly for

development of the peripheral nervous system. • Cells split off from the neural tube as it closes,

and nociceptors grow from the dorsal part of this neural crest tissue.

• Forms late during neurogenesis.

Nociceptor• Sensory input from various stimuli (either

external or internal) is received by specific peripheral receptors, called as nociceptors.

• Nociception – responds as transducers and transmit impulses.

• Perception of pain.• Found in all areas of body.

• External nociceptors – skin, cornea and mucosa. • Internal nociceptors – muscle, joint, bladder, gut and

continuing along the digestive tract. • Cell bodies of these neurons are located in either

the dorsal root ganglia or the trigeminal ganglia. • Trigeminal ganglia are specialized nerves for the face,

whereas the dorsal root ganglia associate with the rest of the body.

TRACT SITUATION FUNCTIONAnterior

spinothalamic tractAnterior white

funiculusCrude touch

sensationLateral spinothalamic

tract Lateral white funiculus

Pain and temperature sensation

Ventral spinocerebellar tract

Subcutaneous kinaesthetic

sensationDorsal

spinocerebellar tractSubcutaneous kinaesthetic

sensationSpinotectal tract Concerned with

spinovisual reflexFasiculus

dorsolateralisPain and temperature

sensationSpinoreticular tract Consciousness and

awarenessSpinoolivary tract Proprioception

Spinovestibular tract ProprioceptionFasiculus gracilis Posterior white

funiculusTactile sensation,

localization, discrimination

Vibratory, conscious kinaesthetic, stereognosis

sensation

Fasiculus cuneatus

Ascending pathways

SOMATOSENSORY CORTEX

Sensory Neurons

Neospinothalamic fibresPaleospinothalamic fibres

Descending pathwaysTRACT SITUATION FUNCTION

Pyramidal Tracts

Anterior corticospinal

tract

Anterior white funiculus Voluntary movements

Lateral corticospinal

tract

Lateral white funiculus

Extrapyramidal Tracts

Medial longitudinal Fasciculus

Anterior white funiculus Coordination of reflex-ocular movements and integration of

movements of eyes and neck

Anterior vestibulospinal

tract

Anterior white funiculus Maintains muscle tone and posture

Position of head and body during

accelerationLateral

vestibulospinal tract

Lateral white funiculus

Reticulospinal tract

Lateral white funiculus Controls voluntary and reflex movements,

muscle tone, respiration and blood vessels

Tectospinal tract

Anterior white funiculus Movement of head in response to visual

and auditory impulsesRubrospinal

tractLateral white funiculus Facilitatory influence on

flexor muscle toneOlivospinal tract Lateral white funiculus Movements arising due to

proprioception

Neurophysiology of Pain

Transduction• Activation of nociceptor.1.Intense thermal and mechanical stimuli, noxious

chemicals, noxious cold2.Stimulation of inflammatory mediators• Damaged tissue release bradykinin, potassium,

histamine, serotonin and arachidonic acid.• Arachidonic acid produce prostaglandins and

leukotrienes.

• Bradykinin + Leukotriene + Prostaglandin

Plasma extravasation

Edema

• PG stimulate nociceptors directly.

• LK stimulates nociceptors indirectly by PMNs

Release chemical mediators

Stimulates nociceptor• BK causes sympathetic nerve terminal

to release PG thus stimulates nociceptor.

• Sympathetic nerve terminal release another PG in response to its own neurotransmitter (norepinephrine).

• Such ongoing inflammatory state causes physiologic sensitization of nociceptors thus generating a response even to a non-painful stimuli and exaggerated response to noxious stimuli.

Transmission• Process by which peripheral nociceptive

information is relayed to CNS. • First order neuron synapses with the secondary

order neuron from where impulse is carried to higher structures of brain.

• Repeated or intense C fibre activation brings specific changes on N-methyl-D-aspartate receptors resulting in central sensitization, thus, response of secnd order neurons increases as well as size of the receptive field also increases.

Modulation• It is the mechanism by which transmission of

impulse to the brain is reduced. • Nociceptive transmission is influenced by : a)Descending inhibitory systems that originate

supraspinallyb)Periaqueductal grayc)Nucleus raphe magnusd)Nucleus tractus solitariuse)Locus ceruleus/subceruleusf)Endogenous opioid peptides

• Endogenous opioid peptides are naturally occurring pain-dampening neurotransmitters and neuromodulators employed in suppression and modulation of pain because they are present in large quantities in areas of brain associated with these activities.

Perception

• It is the subjective experience of pain. It is the sum of complex activities in CNS that may shape the character and intensity of pain perceived and ascribe meaning to pain.

Theories of pain

• Intensity Theory• Specificity Theory • Pattern Theory• Gate Control Theory 

Intensity theory• Erb in 1874. • Pain is a non-specific sensation and is produced

only during high intensity stimulation.• Not accepted – Trigeminal neuralgia, patient

can suffer excruciating pain even when the stimulus is no greater than gentle touch provided it is applied in trigger zone.

Specificity theory• Von Frey in 1895. • Body has a separate sensory system for perceiving pain,

just as it does for hearing and vision i.e. Meissner corpuscles - touch, Ruffini end organs - warmth, Krause end organs - cold, nociceptors – pain.

• Disapproved - it does not account for the wide range of psychological factors that affect our perception of pain.

Pattern theory• Goldschneider in 1920.• There is no separate system for perceiving pain and pain

receptors are shared with other senses, such as of touch. • Peripheral sensory receptors, responding to touch,

warmth and other non-damaging as well as to damaging stimuli, give rise to non-painful or painful experiences as a result of differences in the patterns of the signals sent through the nervous system.

Gate control theory• Ronald Melzack and Patrick Wall in 1965.• Variation in relative input of neural impulse along large and

small fibres.• Small fibres - relay impulses to the cells of substantia gelatinosa• Large fibres relay impulses - marginal cells of posterior gray

horn because cells of substantia gelatinosa terminate on small fibres just when large fibres are about to synapse on it, thus resulting in reduction / stoppage in the ongoing activity of impulse transmission.

• Large fibres has the ability to modulate synaptic transmission of small fibres within the dorsal horn.

• Large fibres creates a hypothetical gate that can open or close the system to pain stimulation.

3 factors for opening and closing of gate:• Amount of activity in pain fibres.• Amount of activity in peripheral fibres - These fibers are called

as Aβ fibres and carry information about harmless stimuli or mild irritation such as touching, rubbing, or lightly scratching the skin. Activity in these fibers tends to close the gate in the presence of noxious stimuli and thus inhibits the pain perception. This explains relief of pain when gentle massage or heat is applied to sore muscles.

• Impulses that descends from the brain – Impulses sent by neurons located in brainstem and cortex can open or close the gate. The effects of some brain processes opens or closes the gate for all inputs from any areas of the body. But the impact of other brain processes may be very specific, applying to only some inputs from certain parts of the body. This explains the fact that people who are hypnotized or distracted, by competing environmental stimuli, may not notice the pain of injury.

Management of painNon-pharmalogical interventions• Bed rest• Distraction• Therapeutic modalitiesa. TENSb. Superficial heatc. Ultrasoundd. Cryotherapye. Acupuncture• Exercise• Hypnosis Pharmacologic interventions• Non-opioids analgesics• Opioids analgesics

NON PHARMACOLOGICAL

MANAGEMENT

• Bed rest – Bed rest may be beneficial to allow for reduction of significant muscle spasm brought on with upright activity.

• Distraction – It is nothing but just diversion of one’s attention from pain to something else as people has a ability to turn their attention away from objects and events.

• TENS (Transcutaneous Electrical Nerve Stimulation) – It is the local stimulation of sore sites and strong neurologic sites in the region of pain, followed by stretching of the stiff muscle. Electrodes are placed directly on the skin.

• Chronic pain conditions not in acute pain.

• Superficial heat – It is superficial heating modality limited to a depth of 1-2 cm. Deeper tissues are not heated because of the thermal insulation of subcutaneous fat and increased blood flow that dissipates heat. It diminishes the pain and decreases local muscle spasm. There is a new emerging concept among it is Continuous low level heat therapy that allows for active use of therapeutic heat resulting in pain reduction, decreased muscle stiffness, improved flexibility, and decreased disability.

• Ultrasound – It is a deep heating modality and is effective in heating structures where superficial heat cannot reach.

• Not indicated in acute inflammatory conditions where it may severe or exacerbate the inflammatory response.

• Cryotherapy – It is the reduction of intramuscular temperature to 3O - 7OC by application of cold. It works by decreasing nerve conduction velocity along pain fibres with a reduction of muscle spindle activity responsible for mediating local muscle tone. It can be achieved by application of ice

• Applied over a region for 15-20 min and 3-4 times/day.

• Acute phase of treatment.

• Acupuncture – Most common form of strong counterstimulation.

• Chronic pain. • Local needling in sore sites and strong

neurologic sites in the region. 30 min of low frequency electrical stimulation i.e. 2-3 Hz is added by clipping the stimulator directly to the inserted needle.

• Hypnosis – Application of techniques of attention modification, paced breathing and muscle relaxation. The process of helping a patient to reach hypnotic state is called induction.

PHARMACOLOGICAL MANAGEMENT

WHO analgesic ladder, 1986

• Adjuvants include antidepressants, antiepileptics, sodium channel blockers.

Nonselective COX inhibitors• Salicylates: aspirin• Propionic acid derivatives: ibuprofen• Anthranilic acid derivatives: mephenamic acid• Aryl-acetic acid derivatives: diclofenac• Oxicam derivatives: piroxicam• Pyrrolo-pyrrole derivative: ketorolac• Indole derivative: indomethacin• Pyrazolone derivatives: phenylbutazonePreferential COX-2 inhibitors• Nimesulide, meloxicam, nabumetoneSelective COX-2 inhibitors• Celecoxib, valdecoxibAnalgesic-antipyretics with poor anti-inflammatory action• Paraaminophenol derivative: paracetamol• Pyrazolone derivatives: metamizol• Benzoxazocine derivative: nefopam

• PG, prostacyclin and thromboxane A2 are produced from arachidonic acid by enzyme cyclooxegenase which exists in the constitutive(COX-1) and inducible(COX-1) isoforms. Non opioid analgesics inhibits COX-1 COX-2 nonselectively or COX-2 selectively.

• Salicylates acts by obtunding peripheral pain receptors and prevents PG mediated sensitization of nerve endings. They raise the threshold to pain perception.

• Propionic acid derivatives inhibit PG synthesis, platelet aggregation and prolongs bleeding time.

• Anthranilic acid derivatives inhibits COX and antagonise certain actions of PGs.

• Aryl-acetic acid derivatives inhibits PG synthesis and has short lasting antiplatelet action.

• Oxicam derivatives lowers PG concentration in synovial fluid and inhibits platelet aggregation.

• Pyrrolo-pyrrole derivative and Indole derivative inhibits PG synthesis.• Selective COX-2 inhibitors inhibits only COX-2 without affecting COX-1

function. They do not depress thromboxane A2 production by platelets thus platelet aggregation remains undepressed but reduce PG production by vascular endothelium.

Opioids

• Natural opium alkaloids: morphine, codeine

• Semisynthetic opiates: diacetylmorphine, pholcodeine

• Synthetic opiods: pethidine, fentanyl, tramadol

• Opioid analgesics exert their actions by interacting with specific receptors present on neurons in CNS and in peripheral tissues. They inhibit the release of excitatory transmitters from primary afferents carrying impulses.

• Action at supraspinal sites in medulla, midbrain, limbic and cortical areas alter processing and interpretation of pain impulses and send inhibitory impulses through descending pathways to the spinal cord.

• Mu receptors are located widely throughtout the CNS especially in the limbic system and thalamus, striatum, hypothalamus and midbrain.

• Kappa receptors are located primarily in the spinal cord and cerebral cortex.

• Delta receptors are mainly present in dorsal horn of spinal cord.

Antidepressants1. Reversible inhibitors of MAO-A: Moclobemide2. Tricyclic antidepressantsa. NA + 5-HT reuptake inhibitors: imipramineb. Predominantly NA reuptake inhibitors:

desipramine3. Selective serotonin reuptake inhibitors:

fluoxetine, sertraline4. Atypical antidepressants: trazodone,

mianserin

• It is known that descending pain modulation pathways release serotonin (5-hydroxytryptamine or 5-HT) and norepinephrine (NE) to suppress pain transmission.

• The depressed patient has a dysfunctional 5-HT or NE system implying a dysfunctional pain modulation pathway.

• This explains comorbid pain symptoms in patients with depression.

Antiepileptics• Barbiturate: phenobarbitone• Deoxybarbiturate: primidone• Hydantoin: phenytoin• Iminostilbene: carbamazepine• Succinimide: ethosuximide• Aliphatic carboxylic acid: valproic acid• Benzodiazepines: diazepam• Phenyltriazine: lamotrigine• Cyclic GABA analogue: gabapentin• Newer drugs: vigabatrin

• They limit neuronal excitation and enhance inhibition. Various sites of action include CNS voltage-gated ion channels involved in pain transmission (i.e. sodium and calcium channels), the excitatory receptors for glutamate including N-methyl-D-aspartate receptors, and the inhibitory receptors for GABA and glycine.

Clinical aspectsTooth ache • Pulpitis (acute / chronic)• Periapical pathology• Trauma

ManagementNSAIDS followed by RCT / Extraction

Temporomandibular disorders – Limitation of opening, episodes of joint locking, pain with mandibular dysfunction, facial pain and headache.

Management• Physical therapy• Pharmacotherapy - analgesics, nonsteroidal anti-inflammatory

drugs (NSAIDs), local anesthetics, oral and injectable cortico steroids, sodium hyaluronate injections, muscle relaxants, botulinum toxin injections, and antidepressants.

• NSAIDS - Commonly used NSAIDs include ibuprofen and naproxen, celecoxib.

• Local anesthetics – They are primarily used when a myofascial trigger point is present. Myofascial trigger points are usually detected in the mastication muscles. The trigger point injection technique involves locating the trigger point, which is usually found in a taut band of muscle, and needling the area.

• TMJ injections - Intracapsular injection of corticosteroids significantly reduces TMJ pain. It is indicated for acute and painful arthritic TMJ that has not responded to other modalities of treatment. Triamcinolone or dexamethasone, in addition to 2% lidocaine without epinephrine is used.

• The quantity of steroid injections should be carefully considered due to the possibility of bone resorption in the site of injection.

• Muscle relaxants – It can be prescribed for acute muscle tension associated with TMJ disorders. A commonly used and effective muscle relaxant is cyclobenzaprine, started at lower dosages (5–10 mg) and taken 1–2 hours before bedtime.

• Antidepressants - Tricyclic antidepressants like amitriptyline and nortriptyline. They have anti-nociceptive effects.

• Occlusal appliance therapy – They are processed acrylic devices that are used for the purpose of equally distributing jaw parafunctional forces, reducing the forces placed on the masticatory muscles, and protecting the occlusal surfaces of the teeth from chronic nocturnal bruxing.

• Surgical intervention - When non-surgical therapy has been ineffective, surgical recommendations, such as arthrocentesis and arthroscopy, depend on the degree of internal derangement.

1.Arthrocentesis is a conservative treatment that involves an intra-articular lavage with or without deposit of corticosteroids that is useful when there are intra-articular restrictions to movement.

2. Arthroscopy is a closed surgical procedure that is useful in hypomobility due to joint derangement58 as well as fibrosis.

3. Arthrotomy is an open surgical procedure that modifies joint anatomy.

• Acupuncture – It involves the stimulation of acupuncture points that are thought to stimulate the flow of energy believed to be blocked.

Trigeminal neuralgia – It is a chronic paroxysmal neuropathic pain condition that is described as a severe, lancinating, and electric-like unilateral pain.

• There is usually a trigger zone in the trigeminal distribution which, when stimulated, can result in an excruciatingly painful attack.

• The etiology is vascular compression that may result in focal demyelination. The superior cerebellar artery compression on the trigeminal root is responsible for attacks of TN pain.

Management• Pharmacological intervention – Antiepileptic

medications are the drugs of choice for the management of TN.

• First-line medications – Carbamazepine, Oxcarbazepine, and Gabapentin

• Second-line medications – Baclofen and Lamotrigine

• Surgical intervention – If pain attacks recur and medications are no longer effective, neurosurgical options such as microvascular decompression or gamma knife radiosurgery may be considered.

Glossopharyngeal neuralgia – It is a rare condition associated with pain in the area supplied by the glossopharyngeal nerve including nasopharynx, posterior part of the tongue, throat, tonsil, larynx, and ear.

Management• Pharmacological intervention – Antiepileptic

medications are the drugs of choice for the management.

• Surgical intervention – If medication management fails, then microvascular decompression, radiofrequency thermocoagulation, gamma knife radiosurgery, or rhizotomy.

Peripheral trigeminal neuropathic pain – It can arise as a result of a traumatic nerve injury resulting in chronic aching, continuous burning like pain at the site of the injury.

Management• Topical medications can be used. Capsaicin is a common locally

acting pharmacologic agent that can be utilized in cream or gel form, normally at a concentration ranging from 0.025%–0.05% mixed with benzocaine 20% and applied with

the use of a stent that covers the affected area (neurosensory stent). •Cream may also include analgesics/sedatives such as ketamine, NSAIDs such as diclofenac, anticonvulsant drugs such as gabapentin and carbamazepine, and tricyclic antidepressant medications such as nortriptyline and amitriptyline.

Centralized trigeminal neuropathic pain - Prolonged stimulation of peripheral nociceptors may eventually lead to central neural changes. The pain in these cases is described as continuous, aching, and burning.

Management• Centrally acting systemic medications are used.

Antiepileptic drugs, such as gabapentin and valproic acid, in combination with tricyclic antidepressants such as amitriptyline, may reduce pain.

Atypical odontalgia – It is a centralized trigeminal neuropathy often localized in a tooth or tooth area.

Management• If the pain is localized to a peripheral origin, a topical

medication can be used and a neurosensory stent can be fabricated. Systemic approaches such as tricyclic antidepressants, calcium channel blockers (pregabalin and gabapentin), sodium channel blockers (carbamazepine), and antiepileptics such as topiramate can be used.

References• Human physiology 3rd edition

- by Prof A K Jain• Concise medical physiology 5th edition

- by Sujit K Chaudhari• Essentials of medical physiology 2nd edition

- by K Sembulingam• Monheims local anesthesia and pain control

in dental practice 7th edition- by C Richard Bennett

• Oral and Maxillofacial Surgery Clinics of North America – Orofacial pain and Dysfunction .(Volume 2008, Number 2, May 2008)

• Non pharmacologic management of pain – Journal of American Osteopathic Association (Supplement 8, Volume 104, Number 11, November 2004)

• Commentary article on “Is theWHO analgesic ladder still valid?” – Canadian family physician (Volume 56, Page 514-517, June 2010)

• Journal of pain research – Orofacial pain management : current prospectives (Volume 7, Pages 99-115, Year 2014)

Thank you