1. How can we reduce acute and chronic
peripheral neuropathic pain?
Dr Stephen Humble
Consultant in Pain Management
& Anaesthesia, Charing Cross Hospital
QUT15040UKb September 2015
2. 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
3. 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
4. Neuropathic Cancer Pain
• Chemotherapy
• Radiotherapy
• Post surgical resection
• Peripheral nerve invasion
• Spinal cord compression
• Paraneoplastic syndromes
Lema et al., 2010 The Oncologist
6. 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
7. 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
8. 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
9. 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
10. 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?
11. 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
13. Methods 2
Inclusion 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
14. 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)
15. 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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*
*
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16. Gabapentin did not reduce the incidence or intensity of
postamputation pain in vascular patients with chronic pain
Nikolajsen et al., 2006
17. Paravertebral block reduced chronic pain
after mastectomy
Kairaluoma et al., 2006
Prevalence of significant pain
(VAS > 3)
Sham block
Paravertebral block
18. Cryoanalgesia is ineffective for preventing
CPSP in thoracotomy
Lu et al., 2013
Pain scores Analgesic consumption
19. Higher dose Remifentanil associated with larger area
of allodynia post thoracotomy
Salengros et al., 2010
20. 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.
21. 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.
22. Discussion 1
Several 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
23. 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
24. 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
25. Implications & practical steps
1. Screening & identifying patients early
2. Perioperative use of routine anti-neuropathic pain drugs
1. Additional options
26.
27. Imperial Clinical pathway for high strength capsaicin patch therapy
Must have peripheral NP
i.e. allodynia /hyperalgesia
Dorset Naga
~1,000,000 SHU
28. 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
29. The End
• Thank you for listening!
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