How can we reduce acute and chronic peripheral neuropathic pain?

Dr Stephen HumbleConsultant in Pain Management & Anaesthesia, Charing Cross Hospital

QUT15040UKb September 2015

Introduction

• Anaesthesia is 3rd greatest medical advance since 1840• Treatment of chronic neuropathic pain is not as successful !• Prevalence of chronic pain (19%) higher than asthma (5-10%)• Peripheral neuropathic pain accounts for a significant proportion• Chronic Post Surgical Pain (CPSP) is a major issue• Limited therapeutic approaches, but improving

Epidemiology

• Chronic pain 19% of Europeans (Breivik et al., 2006 EJP)• CPSP 5-85% after surgery (Macrae 2008 Pain)• Cancer NeuP 19-39% in cancer pain (Smith et al., 2014 Curr Pain

H R)• Neuropathic Pain 7-10% (van Hecke et al., 2014 Pain)

– Postherpetic neuralgia– Phantom limb pain – Painful diabetic neuropathy

Neuropathic Cancer Pain

• Chemotherapy• Radiotherapy• Post surgical resection• Peripheral nerve invasion• Spinal cord compression• Paraneoplastic syndromes

Lema et al., 2010 The Oncologist

Knee replacement ~5%

Transition: Acute to Chronic

• Intensity of acute postoperative pain correlates with the risk of developing chronic pain

• Henrick Kehlet, The Lancet , 2006– Surgical techniques that minimise nerve injury– Aggressive analgesia– Regional anaesthesia has potential to minimise sensitisation

Acute and Chronic Neuropathic Pain

• Traditionally seen as long term condition• Research focuses on chronic pain• All conditions must have an initial acute phase• Treatment of acute neuropathic pain is extrapolated from

chronic pain

You mean my whole fallacy is wrong?

• “Acute pain is only nociceptive”– Phantom limb pain– Spinal injury pain– Post thoracotomy pain– Post herpetic neuralgia

• “Chronic pain is neuropathic”– Low back pain– Rheumatoid arthritis – Osteoarthritis

Evidence for Mx of perioperative neuropathic pain

• Relative lack of evidence of benefit• Not evidence of lack of benefit• Numerous studies on pre-emptive analgesia for nociceptive

pain (inconclusive)• Relatively few studies for pre-emptive analgesia for

perioperative neuropathic pain

Questions

• What should we use to minimise the risk of chronic post-surgical pain in‘high-risk’ procedures?

• What is the evidence to guide management?

Other Systematic Reviews for CPSP

• Andreae 2013 Systematic review 23 studies– R.A. may reduce CPSP

• Clarke et al., 2012 Meta analysis 11 studies mixed surgery– Gabapentinoids may be effective

• McNicol et al., 2014 Meta analysis 17 studies – Ketamine ineffective

• Marques et al., 2014 Meta analysis 13 studies (THR & TKR)– L.A. infiltration effective for short term

2015

Methods 1

Thoracotomy MastectomyAmputation

Methods 2Inclusion criteria:

•Operations associated with high incidence acute / periop / chronic neuropathic pain

(amputation, mastectomy & thoracotomy)

•RCTs•CRoB tool•Appropriately powered•Periop data•> 2 months follow up

Results• 598 hits identified via Medline, Embase, Cochrane Library & manual tracking

(1946-2014)• 32 RCTs met inclusion criteria• Trial methodology too heterogenous to permit meta-analysis & some trials had

multiple interventions• Trial medications were often given once only or at sub-therapeutic doses

Interventions included:

Gabapentinoids (5) Regional techniques (8)

Anti-depressants (1) Cryoanalgesia (6)

Ketamine (6) Opioids (4)

Local anaesthetic (6) TIVA (1)

Gabapentin 1600mg/day for one week and local anaesthetic reduced incidence of chronic pain at 3 months

Fassoulaki et al., 2005

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Gabapentin did not reduce the incidence or intensity of postamputation pain in vascular patients with chronic pain

Nikolajsen et al., 2006

Paravertebral block reduced chronic pain after mastectomy

Kairaluoma et al., 2006

Prevalence of significant pain (VAS > 3)

Sham blockParavertebral block

Cryoanalgesia is ineffective for preventing CPSP in thoracotomy

Lu et al., 2013

Pain scores Analgesic consumption

Higher dose Remifentanil associated with larger area of allodynia post thoracotomy

Salengros et al., 2010

Interventions 1

• Gabapentinoids reduced pain after mastectomy, but a single dose was ineffective for thoracotomy patients who had an epidural.

• Gabapentinoids were ineffective for vascular amputees with pre-existing chronic pain.

• Venlafaxine was associated with less chronic pain after mastectomy.

• The majority of the trials investigating regional anaesthesia found it to be beneficial for reducing chronic symptoms.

Interventions 2

• Intravenous and topical lidocaine and perioperative EMLA cream reduced the incidence of chronic pain after mastectomy

• Local anaesthetic infiltration appeared ineffective.

• Ketamine offered no reduction in chronic pain.

• Intercostal cryoanalgesia offered no reduction in chronic pain.

• TIVA reduced the incidence of post-thoracotomy pain in one study, whereas high-dose remifentanil exacerbated chronic pain in another.

Discussion 1Several consistent themes emerged:

•Acute pain in the perioperative period after amputation, mastectomy and thoracotomy appears to be a mix of nociceptive and neuropathic pain

•Acute neuropathic component – is potentially responsive to agents that work on neuropathic symptoms, but not nociceptive

symptoms– may be relatively resistant to conventional analgesics– is potentially treatable if correct dose/duration/timing

•Neuropathic symptoms may take several days to manifest•Therefore the days following an operation appear to be as important as the day of the operation itself

Discussion 2

• Acute/perioperative neuropathic pain is under-recognised

• Appropriate doses of gabapentinoids, antidepressants, regional anaesthesia may reduce the severity of neuropathic pain for patients undergoing high-risk operations such as amputation, thoracotomy and mastectomy

• Ketamine & Intercostal cryoanalgesia are ineffective at reducing chronic pain

• If (vascular) patients had chronic pain pre-op they also had it post-op

• High dose opioids may be detrimental

Discussion 3• The choices that anaesthetists make may have long-term implications• A pragmatic approach should be taken until further evidence appears• Anaesthetists should not bury their head in the sand and or rely on

ineffective techniques

• Appropriately high dosages of medications• Therapy could commence prior to surgery & continue for weeks. • RCT Follow-up > 6 months

• May decrease the burden on society and the amount of financial resources spent on the Mx of chronic pain

Implications & practical steps

1. Screening & identifying patients early

2. Perioperative use of routine anti-neuropathic pain drugs

1. Additional options

Imperial Clinical pathway for high strength capsaicin patch therapy

Must have peripheral NPi.e. allodynia /hyperalgesia

Dorset Naga~1,000,000 SHU

Summary• Neuropathic pain has significant societal impact• Many causes of NeuP

Including CPSP and cancer• We should use standardised tools for identifying NeuP• Limited treatment options but some cause for optimism• Increasing evidence for high strength capsaicin patch

• Acute perioperative neuropathic pain–is potentially responsive to agents that work on neuropathic symptoms, but not nociceptive symptoms–may be relatively resistant to conventional analgesics–is potentially treatable if correct dose/duration/timing

• Anaesthetists should take a pragmatic approach until further evidence appears

The End

• Thank you for listening!

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