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Recent Advances in the Pharmacological Management of Neuropathic Pain

  • Pain Medicine (GJ Meredith, Section Editor)
  • Published:
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Abstract

Chronic neuropathic pain (NeP) is common. Traditional pharmacological treatments can demonstrate surprisingly little efficacy for reducing pain scores or improving function, and their use is often limited by side effects. Research into chronic pain pathophysiology has expanded in recent years and only by understanding these underlying mechanisms will we be best placed to develop new and novel drug therapies. In this review article, we will highlight some of the more recent pharmacological agents that have established themselves in the pain physicians’ armamentarium and continue to gain popularity as the evidence base grows together with some of the supporting evidences for their use. It is anticipated that this article will act to bring to the forefront of the pain physicians’ mind some of the alternative therapies for the management of chronic NeP that are often thought of as tertiary- or even quaternary-line in many established guidelines.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. http://www.iasp-pain.org/Taxonomy (accessed 8th May 2016).

  2. National Institute for Health and Care Excellence (NICE). Neuropathic pain in adults: pharmacological management in non-specialist settings (CG173) December 2014. https://www.nice.org.uk/guidance/cg173 (accessed 8th May 2016). NICE are the principle body responsible for offering evidence-based advice and guidance on a range of healthcare-related issues to the National Health Service (NHS) in England and Wales. Their guidance CG173 is a comprehensive review of treatments for neuropathic pain in adults using the very best quality evidence at that time.

  3. Saxena AK, Azad R. Advances in the mechanisms, diagnosis and management of neuropathic pain: current opinions and future perspectives. Indian J Anaesth. 2006;50(4):249–57.

    Google Scholar 

  4. Dray A. Neuropathic pain: emerging treatments. Br J Anaesth. 2008;101(1):48–58.

    Article  CAS  PubMed  Google Scholar 

  5. Scottish Intercollegiate Guidelines Network (SIGN). Management of chronic pain: a national clinical guideline (SIGN 136) December 2013. http://sign.ac.uk/guidelines/fulltext/136 (accessed 8th May 2016). SIGN develops evidence-based clinical practice guidelines for the National Health Service (NHS) in Scotland. They are of high quality employing a rigorous systematic review of the scientific literature and are designed as a vehicle for accelerating the translation of new knowledge into action to meet their aim of reducing variations in practice and improving patient-important outcomes.

  6. Bridges S. Chronic Pain. Craig R, Mindell J, eds. Health Survey for England 2011. Leeds: Health and Social Care Information Centre 2012. http://digital.nhs.uk/catalogue/PUB09300/HSE2011-All-Chapters.pdf (accessed 8th May 2016).

  7. Doth AH, Hansson PT, Jensen MP, Taylor RS. The burden of neuropathic pain: a systematic review and meta-analysis of health utilities. Pain. 2010;149:338–44.

    Article  PubMed  Google Scholar 

  8. Dworkin RH, Malone DC, Panarites CJ, Armstrong EP, Pham SV. Impact of postherpetic neuralgia and painful diabetic peripheral neuropathy on health care costs. J Pain. 2010;11(4):360–8.

    Article  PubMed  Google Scholar 

  9. DiBonaventura MD, Cappelleri JC, Joshi AV. Association between pain severity and health care resource use, health status, productivity and related costs in painful diabetic peripheral neuropathy patients. Pain Med. 2011;12(5):799–807.

    Article  PubMed  Google Scholar 

  10. Torrance N, Smith BH, Bennett MI, Lee A. The epidemiology of chronic pain of predominantly neuropathic origin: results from a general population survey. J Pain. 2006;7:281–9.

    Article  PubMed  Google Scholar 

  11. Smith BH, Torrance N, Bennett MI, Lee AJ. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain. 2007;23:143–9.

    Article  PubMed  Google Scholar 

  12. Smith BH, Lee J, Price C, Baranowski AP. Neuropathic pain: a pathway for care developed by the British pain society. Br J Anaes. 2013;111(1):73–9 This Map of Medicine care pathway for the management of neuropathic pain was led by internationally renowned group acting on behalf of the British Pain Society. Not only does it take into consideration the scientific evidence in its recommendations but also opinion of experts in the field producing a practical solution to management of neuropathic pain.

    Article  CAS  Google Scholar 

  13. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289–305.

    Article  CAS  PubMed  Google Scholar 

  14. Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2012; 9.

  15. Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013:2 .The Cochrane Group is a global independent network of research professionals. They have produced meta-analysis of high quality RCTs related to topical capsaicin use.

  16. Darré L, Domene C. Binding of capsaicin to the TRPV1 Ion Channel. Mol Pharm. 2015;12(12):4454–65.

    Article  CAS  PubMed  Google Scholar 

  17. Jaggi AS, Khan N, Singh N. Possible role of spleen derived factors, vanilloid receptors and calcitonin gene-related peptide in diabetes induced hyperalgesia in mice. Pharm Soc Jap. 2008;128(11):1699–705.

    Article  Google Scholar 

  18. Sokabe T, Tominaga M. Molecular mechanisms underlying thermosensation in mammals. Brain Nerve. 2007;61:867–73.

    Google Scholar 

  19. Mandadi S, Roufogalis BD. ThermoTRP channels in nociceptors: taking a lead from capsaicin receptor TRPV1. Neuropharmacol. 2008;6:21–38.

    Article  CAS  Google Scholar 

  20. Schumacher M, Pasvankas G. Topical capsaicin formulations in the management of neuropathic pain. Prog Drug Res. 2014;68:105–28. This paper critically reviews the evidence for capsaicin use in neuropathic pain. Its authors are well renowned in their respective fields and present their case in a logical and well-balanced fashion.

    CAS  PubMed  Google Scholar 

  21. Bley K. Effects of topical capsaicin on cutaneous innervation: implications for pain management. The Open Pain Journal. 2013;6:81–94. This review sets out very clearly the mechanistic theories behind nerve fiber desensitization with capsaicin use and the basic science studies supporting these.

    Article  CAS  Google Scholar 

  22. Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8 % patch. Br J Anaesth. 2011;107:490–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Committee for Medicinal Products for Human Use (CHMP). European Public Assessment Report—Qutenza. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000909/WC500040448.pdf (accessed 8th May 2016).

  24. Maihofner C, Heskamp M. Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8 % cutaneous patch in 1044 patients with peripheral neuropathic pain: first results of the QUEPP study. Curr Med Res Opin. 2013;29:673–83. Well-designed study showing efficacy for capsaicin patch up to 12 weeks.

    Article  CAS  PubMed  Google Scholar 

  25. Assessment report (licence extension). Qutenza®, capsaicin. 23 July 2015. EMA/545605/2015. Committee for Medicinal Products for Human Use (CHMP). www.ema.europa.eu (accessed 8th May 2016).

  26. Summary of Product Characteristics. Qutenza® 179 mg cutaneous patch (capsaicin). Last updated on eMC: 23/09/2015. Astellas Pharma Limited. www.medicines.org.uk (accessed 8th May 2016).

  27. Stoker M, Jacobs H, Lloyd A. Double-blind, randomised, placebo controlled study of the efficacy and safety of capsaicin 8 % cutaneous patch (Qutenza®) in patients with painful diabetic neuropathy: STEP study. 5th International Congress on Neuropathic Pain (NeuPSIG), Nice; 2015.

  28. Vinik A, Perrot S, Vinik E. Long-term safety and efficacy of repeated applications of capsaicin 8 % patch (Qutenza®) in painful diabetic peripheral neuropathy: PACE study. 5th International Congress on Neuropathic Pain (NeuPSIG), Nice; 2015.

  29. Jacobs H, Stoker M, Long S, et al. Long-term safety of repeated applications of capsaicin 8 % patch (Qutenza®) plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: PACE study. 5th International Congress on Neuropathic Pain (NeuPSIG), Nice; 2015.

  30. Snijder R, Stoker M, Long S. Sustained efficacy of repeated applications of capsaicin 8 % patch (Qutenza®) plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: PACE study. 5th International Congress on Neuropathic Pain (NeuPSIG), Nice; 2015.

  31. Acorda Therapeutics, Inc. Qutenza: Treatment Guide. Available from: http://www.qutenza.com/_docs/Qutenza%20Treatment%20Guide.pdf (accessed 8th May 2016).

  32. Mick G, Correa-Illanes G. Topical pain management with the 5 % lidocaine medicated plaster—a review. Curr Med Res Opin. 2012;28:937–51.

    Article  CAS  PubMed  Google Scholar 

  33. Campbell BJ, Rowbotham M, Davies PS, Jacob P, Benowitz NL. Systemic absorption of topical lidocaine in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. J Pharm Sci. 2002;91:1343–50.

    Article  CAS  PubMed  Google Scholar 

  34. Baron R, Mayoral V, Leijon G. Efficacy and safety of combination therapy with 5 % lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin. 2009;25:1677–87.

    Article  CAS  PubMed  Google Scholar 

  35. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237–51.

    Article  CAS  PubMed  Google Scholar 

  36. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;2:CD004846.

    Google Scholar 

  37. Binder A, Bruxelle J, Rogers P, Hans G, Bösl I, Baron R. Topical 5 % lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig. 2009;29:393–408.

    Article  CAS  PubMed  Google Scholar 

  38. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study. Curr Med Res Opin. 2009;25:1663–76.

    Article  CAS  PubMed  Google Scholar 

  39. Wolff RF, Bala MM, Westwood M, Kessels AG, Kleijnen J. 5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systemic review. Acta Neurol Scand. 2011;123:295–309.

    Article  CAS  PubMed  Google Scholar 

  40. Patch Study Group. Lidocaine patch 5 % reduces pain intensity and interference with quality of life in patients with postherpetic neuralgia: an effectiveness trial. Pain Med. 2002;3:324–32.

    Article  Google Scholar 

  41. Kim JY, Lim WJ, Lee SJ. Efficacy of piroxicam patch compared to lidocaine patch for the treatment of postherpetic neuralgia. Ann Dermatol. 2011;23:162–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rehm S, Binder A, Baron R. Post-herpetic neuralgia: 5 % lidocaine medicated plaster, pregabalin, or a combination of both? A randomized, open, clinical effectiveness study. Curr Med Res Opin. 2010;26:1607–19.

    Article  CAS  PubMed  Google Scholar 

  43. Galer BS, Rowbotham MC, Perander J, Friedman E. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999;80:533–8.

    Article  CAS  PubMed  Google Scholar 

  44. Rowbotham MC, Davies PS, Verkempinck C, Galer BS. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain. 1996;65:39–44.

    Article  CAS  PubMed  Google Scholar 

  45. Covino BG, Wildsmith JA. Clinical pharmacology of local anaesthetic agents. In: Cousins MJ, editor. Neural Blockade. 3rd ed. Philadelphia: JB Lippincott; 1998.

    Google Scholar 

  46. Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr, DB. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev 2005; CD003345.

  47. Argoff CE. New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain. 2000;16(2 Suppl):S62–6.

    Article  CAS  PubMed  Google Scholar 

  48. Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain. 2000;16:205–8.

    Article  CAS  PubMed  Google Scholar 

  49. Baron R, Mayoral V, Leijon G. Efficacy and safety of 5 % lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial. Clin Drug Investig. 2009;29:231–41.

    Article  CAS  PubMed  Google Scholar 

  50. Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85:S3–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Medicine Reports. 2010:2–52.

  52. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;18:CD004846.

    Google Scholar 

  53. Rowbotham MC, Rachel DW, Thomas J, Nothaft W, Backonja MM. A randomized, double- blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain. Pain. 2009;146:245–52.

    Article  CAS  PubMed  Google Scholar 

  54. Glorioso JC, Fink DJ. Herpes vector-mediated gene transfer in the treatment of chronic pain. Mol Ther. 2009;17:13–8.

    Article  CAS  PubMed  Google Scholar 

  55. Schröder W, Vry JD, Tzschentke TM. Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. Eur J Pain. 2010;14:814–21.

    Article  CAS  PubMed  Google Scholar 

  56. Tzschentke TM, Christoph T, Kogel B, et al. (−)-(1R,2R)-3-(3-dimethylamino- 1-ethyl-2-methyl-propyl)-phenol hydro- chloride (tapentadol HCl): a novel mu- opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J of Pharm and Ex Therap. 2007;323:265–76.

    Article  CAS  Google Scholar 

  57. Royal Pharmaceutical Society. British National Formulary No. 64. London: BMJ Group and Pharmaceutical Press; 2012 .http://www.evidence.nhs.uk/formulary/bnf/current/4-central-nervous-system/47-analgesics/472-opioid-analgesics/tapentadol (accessed 8th May 2016)

    Google Scholar 

  58. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27:151–62.

    Article  CAS  PubMed  Google Scholar 

  59. Gibbison B, Bailey CR, Klein AA. Tramadol—the Marmite™ drug. Anaesthesia. 2015;70:125–30.

    Article  CAS  PubMed  Google Scholar 

  60. Tzschentke TM, Christoph T, Kogel B, et al. (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl- propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007;323:265–76.

    Article  CAS  PubMed  Google Scholar 

  61. Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth. 2014;113:148–56.

    Article  CAS  PubMed  Google Scholar 

  62. Christoph T, Schroder W, Tallarida RJ, De Vry J, Tzschentke TM. Spinal-supraspinal and intrinsic mu-opioid receptor agonist-norepinephrine reuptake inhibitor (MOR-NRI) synergy of tapentadol in diabetic heat hyperalgesia in mice. J Pharmacol Exp Ther. 2013;347:794–801.

    Article  CAS  PubMed  Google Scholar 

  63. Schröder W, Tzschentke TM, Terlinden R, et al. Synergistic interaction between the two mechanisms of action of tapentadol in analgesia. J Pharmacol Exp Ther. 2011;337:312–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bee LA, Bannister K, Rahman W, Dickenson AH. Mu-opioid and noradrenergic α(2)-adrenoceptor contributions to the effects of tapentadol on spinal electrophysiological measures of nociception in nerve-injured rats. Pain. 2011;152:131–9.

    Article  CAS  PubMed  Google Scholar 

  65. Raffa RB, Buschmann H, Christoph T, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother. 2012;13:1437–49.

    Article  CAS  PubMed  Google Scholar 

  66. Ramaswamy S, Chang S, Mehta V. Tapentadol—the evidence so far. Anaesthesia. 2015;70:511–27.

    Article  CAS  Google Scholar 

  67. Dworkin RH, Turk DC, Peirce-Sandner S, Baron R, Bellamy N, Burke LB. Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. Pain. 2010;149(2):177–93.

    Article  PubMed  Google Scholar 

  68. Vadivelu N, Huang Y, Mirante B, Jacoby M, Braveman FR, Hines RL, Sinatra R. Patient considerations in the use of tapentadol for moderate to severe pain. Drug Healthcare and Patient Safety. 2013;5:151–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Riemsma R, Forbes C, Harker J, Worthy G, Misso K, Schäfer M, Kleijnen J, Stürzebecher S. Systematic review of tapentadol in chronic severe pain. Curr Med Res Opin. 2011;27:1907–30.

    Article  CAS  PubMed  Google Scholar 

  70. Merchant S, Provenzano D, Mody S, et al. Composite measure to assess efficacy/gastrointestinal tolerability of tapentadol ER versus oxycodone CR for chronic pain: pooled analysis of randomized studies. J Opioid Manag. 2013;9:51–61. Gastrointestinal side effects of opioid analgesia can be a great source of morbidity for some and may even limit effectiveness and compliance. This meta-analysis of RCTs concludes tapentadol’s superiority over oxycodone, which may have a significant clinical advantage in some patient populations.

    Article  PubMed  Google Scholar 

  71. de Leon-Casasola O. New developments in the treatment algorithm for peripheral neuropathic pain. Pain Med. 2011;12v(Suppl 3):S100–8.

    Article  Google Scholar 

  72. Qerama E, Fuglsang-Frederiksen A, Jensen TS. The role of botulinum toxin in management of pain: an evidence-based review. Curr Opin Anaesthesiol. 2010;23:602–10.

    Article  PubMed  Google Scholar 

  73. Howard SS. Botulinum toxins for analgesia. Pain Physician. 2009;12:479–81.

    Google Scholar 

  74. Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64(3):274–83.

    Article  PubMed  Google Scholar 

  75. Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med. 2010;11(12):1827–33.

    Article  PubMed  Google Scholar 

  76. Attal N, de Andrade D, Adam F, et al. Safety and efficacy of repeated injections of botulinum toxin a in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016;15(6):555–65.

    Article  CAS  PubMed  Google Scholar 

  77. Oh H, Chung M. Botulinum toxin for neuropathic pain: a review of the literature. Toxins (Basel). 2015;7(8):3127–54.

    Article  CAS  Google Scholar 

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Correspondence to Peter Keogh.

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Keogh, P., Mehta, V. Recent Advances in the Pharmacological Management of Neuropathic Pain. Curr Anesthesiol Rep 6, 327–333 (2016). https://doi.org/10.1007/s40140-016-0186-1

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