Recent and Emerging Trends in Pharmacotherapy of Neuropathic Pain


  • GMC Patiala, Department of Pharmacology, Punjab, India
  • PGI, Department of Pharmacology, Chandigarh, India


Neuropathic pain is a type of chronic pain caused by a lesion or disease of the somatosensory nervous system. The pathophysiology of neuropathic pain is very complex, not fully understood and different from that somatic pain. It has a deleterious effect on health related quality of life, and leads to increased health-care costs and its management is extremely difficult. The response to currently available treatments is less promising, so newer agents with better efficacy and safety are needed. Currently tricyclic antidepressants and anticonvulsants like gabapentin and pregabalin are considered as the 1st line drugs but these are not able to produce complete relief. Various recent drugs are: high dose capsaicin patch, topical lidocaine, botulinum toxin A, lacosamide, Selective Serotinin Reuptake inhibitorss, NMDA antagonists. Certain new targets like endocannabinoid system and various neurotrophic factors like BDNF, NT3, NT4, and GDNF are undergoing preclinical and clinical trials and their role in the treatment of neuropathic pain is still emerging.


Neuropathic Pain, Nociception, Post Herpetic Neuralgia, Painful Diabetic Neuropathy, Recent Drugs.

Subject Discipline

Pharmacy and Pharmacology

Full Text:


Treede RD, Jensen TS, Campbell JN et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008; 70(18):16301635.

Gore M, Dukes E, Rowbotham DJ, Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings, Eur J Pain 2007; 11(6):652–64.

Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms and management. Lancet 1999; 353: 1959–64.

Meyer RA, Campell JN. Peripheral neural mechanisms of nociception. In:Wall PD, Meltzack R, eds. Textbook of Pain. London: Churchill Livingston; 1994.p.13–44.

Baliki MN, Gehe PY, Apkarain AV et al. Beyond feeling: chronic pain hurts the brain, disrupting the default mode network dynamics. J Neurosci 2008; 28: 1398–403

Finnerup NB, Otto M, McQuay HJ et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118(3):289-305.

Max MB, Culnane M, Schafer SC et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987; 37(4):589-596

Raskin J, Smith TR, Wong K et al. Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. J Palliat Med 2006; 9(1):29-40.

Dharmshaktu P, Tayal V, Kalra BS: Efficacy of antidepressants as analgesics:a review. J Clin Pharmacol 2012; 52(1):6-17.

Stahl SM: Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as alpha (2) delta ligands at voltage-gated calcium channels. J Clin Psychiatry 2004, 65(5):596-597.

Gajraj NM. Pregabalin: its pharmacology and use in pain management. Anesth Analg 2007; 105(6):1805-1815.

McLean MJ. Clinical pharmacokinetics of gabapentin. Neurology 1994; 44(6 Suppl 5):S17-S22.

Stacey BR, Swift JN. Pregabalin for neuropathic pain based on recent clinical trials. Curr Pain Headache Rep 2006; 10(3):179-184.

Chevlen E. Opioids: a review. Curr Pain Headache Rep 2003; 7(1):15-23.

Chou R, Fanciullo GJ, Fine PG et al: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009; 10(2):113-130.

Hollingshead J, Duhmke RM, Cornblath DR: Tramadol for neuropathic pain. Cochrane Database Syst Rev 2006; 3:CD003726.

Dworkin RH, O’Connor AB, Backonja M et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132(3):237-251.

Simpson DM, Brown S, Tobias J. NGX4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008; 70:2305– 13.

Backonja M, Wallace MS, Blonsky ER et al. NGX-4010 C116 Study Group. NGX4010, a high concentration capsaicin patch for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol 2009; 7:1106–12.

Backonja MM, Malan TP, Vanhove GF et al.C102/106 Study Group. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension. Pain Med 2010; 11:600–8.

Noto C, Pappagallo M, Szallasi A. NGX4010, a high-concentration capsaicin dermal patch for lasting relief of peripheral neuropathic pain. Curr Opin Investig Drugs 2009; 10(7):702-710.

Xu B, Descalzi G, Ye HR et al. Translational investigation and treatment of neuropathic pain. Molecular Pain 2012; 8(15): 1-8.

Ranoux D, Attal N, Morain F et al. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 2008; 64(3):274-283.

Yuan RY, Sheu JJ, Yu JM et al. Botulinum toxin for diabetic neuropathic pain: a randomized, double-blind crossover trial. Neurology 2009; 72(17):14731478.

Ranoux D. Botulinum toxin and painful peripheral neuropathies: what should be expected? Rev Neurol 2011; 167(1):46-50.

Liu HT, Tsai SK, Kao MC et al. Botulinum toxin. A relieved neuropathic pain in a case of post-herpetic neuralgia. Pain Med 2006; 7(1):89-91.

Piovesan EJ, Teive HG, Kowacs PA et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 2000; 65(8):1306-8.

Argoff CE: New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain 2000; 16(2 S):S62-66.

Baron R, Mayoral V, Leijon G et al. 5% lidocaine medicated plaster versus pregabalin in postherpetic neuralgia and diabetic polyneuropathy: an open label, non-inferiority two-stage RCT study. Curr Med Res Opin2009; 25:1663-76.

Sabatowski R, Hans G, Tacken I et al. Safety and efficacy outcomes of longterm treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia. Curr Med Res Opin 2012; 28(8):1337-46.

Baron R, Mayoral V, Leijon G et al. 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(7):1677-87.

Mick G, Correa-Illanes G. Topical pain management with the 5% lidocaine medicated plaster--a review. Curr Med Res Opin 2012; 28(6):937-51.

Bleakman D, Alt A, Nisenbaum ES. Glutamate receptors and pain. Semin Cell Dev Biol 2006; 17:592–604.

Bennett GJ. Update on the neurophysiology of pain transmission and modulation: Focus on the NMDA receptor. J Pain Symptom Manage 2000; 19:S2–S6.

Carlton SM, Hargett GL, Coggeshall RE. Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. Neurosci Lett 1995; 197:25–8.

Collins S, Sigtermans MJ, Dahan A et al. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Med 2010; 11(11):1726-42.

Jamero D, Vo N, Hawawini F et al. The Emerging Role of NMDA Antagonists in Pain Management. US Pharm 2001; 36(5):HS4-HS8.

Pud D, Eisenberg E, Spitzer A et al. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain 1998; 75:349-354.

Fukui S, Komoda Y, Nosaka S. Clinical application of amantadine, an NMDA antagonist, for neuropathic pain. J Anesth 2001; 15:179-181.

Mecadante S, Casuccio A, Fulfaro F et al. Switching from morphine to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol 2001; 19:2898-2904.

Morley JS, Bridson J, Nash TP et al. Lowdose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med 2003; 17:576-587.

Nikolajsen L, Gottrup H, Kristensen AG et al. Memantine (N-methyl-d-aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double-blinded, cross-over study. Anesth Analg 2000; 91:960-966.

Schifitto G, Yiannoutsos CT, Simpson DM et al. A placebo-controlled study of memantine for the treatment of human immunodeficiency virus-associated sensory neuropathy. J Neurovirol 2006; 12:328-331.

Sang CN, Booher S, Gilron I et al. Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. Anesthesiology 2002; 96(5):1053-61.

McCartney CJ, Sinha A, Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg 2004; 98(5):385-400.

Rowbotham MC, Rachel DW, Thomas J et al. A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain. Pain 2009; 146:24552.

Dworkin RH, O’Connor AB, Audette J et al. Recommendations for the pharmacological management of

neuropathic pain: an overview and literature update. Mayo Clin Pain 2010; 85(3S):S3-S14.

Sindrup SH, Gram LF, Brosen K et al. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain 1990; 42(2):135- 144.

Sindrup SH, Bjerre J, Dejgaard A et al. The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Clin Pharmacol Ther 1992; 52(5):547-552.

Ziegler D, Hidvegi T, Gurieva I et al. Effi cacy and safety of lacosamide in painful diabetic neuropathy. Diabetes Care 2010; 33:839-41.

Shaibani A, Biton V, Rauck R et al. Longterm oral lacosamide in painful diabetic neuropathy: a two-year open-label extension trial. Eur J Pain 2009; 13:45863.

Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fi bromyalgia in adults. Cochrane Database Syst Rev 2012; 2:CD009318.

McCleane G. Pharmacological Management of Neuropathic Pain. CNS Drugs 2003; 17 (14): 1031-1043

Kamei J, Hitosugi H, Kawashima N et al. Antinociceptive effect of mexiletine in diabetic mice. Res Commun Chem Pathol Pharmacol 1992; 77: 245-8.

Wallace MS, Magnuson S, Ridgeway B. Efficacy of oral mexiletine for neuropathic pain with allodynia: a double-blind, placebo-controlled, crossover study. Reg Anesth Pain Med 2000; 25(5):459-67.

Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988; I: 9-11.

Vorobeychik Y, Gordin V, Mao J et al. Combination Therapy for Neuropathic Pain: A Review of Current Evidence. CNS Drugs 2011; 25 (12): 1023-1034.

Mao J, Gold MS, Backonja MM. Combination drug therapy for chronic pain: a call for more clinical studies. J Pain 2011; 12(2):157-66

Gilron I, Max MB. Combination pharmacotherapy for neuropathic pain: current evidence and future directions. Expert Rev Neurother 2005; 5: 823-30

Rao PP, Mohamed T. Current and emerging “at-site†pain medications: a review. J Pain Res 2011; 4:279-86.

Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol 2011; 72:735-44.

Xiong W, Cui T, Cheng K et al. Cannabinoids suppress infl ammatory and neuropathic pain by targeting alpha3 glycine receptors. J Exp Med 2012; 209:1121-34.

Attal N, Martinez V. Recent Developments in the Pharmacological Management of Neuropathic Pain. ENJ 2010; 2(1):22-25.

Levi-Montalcini R. Tissue and nerve growth promoting factors. Biological aspects of specific growth promoting factors. Proc R. Soc Med 1965; 58:357360.

Oppenheim RW, Qin-Wei Y et al. Brain derived neurotrophic factor rescues developing avian moto-neurons from cell death. Nature 1992; 350:755-757.

Taiwo YO, Levine JD, Burch RM et al. Hyperalgesia induced in the rat by the amino-terminal octapeptide of nerve growth factor. Proc Natl Acad Sci USA 1991; 88(12):5144-5148.

Svensson P, Cairns BE, Wang K et al. Injection of nerve growth factor into human masseter muscle evokes longlasting mechanical allodynia and hyperalgesia. Pain 2003; 104(1-2):241247.

Cervero F, Laird JM. Role of ion channels in mechanisms controlling gastrointestinal pain pathways. Curr Opin Pharmacol 2003; 3(6):608-612.

Vivoli E, Salvicchi A, Bartolini A et al. Acetyl-lcarnitine increases artemin level and prevents neurotrophic factor alterations during neuropathy. Neuroscience 2010; 167(4): 1168-1174.

Jing YY, Wang J, Li XL et al. Nerve growth factor of red nucleus involvement in pain induced by spared nerve injury of the rat sciatic nerve. Neurochem Res 2009; 34(9):1612-1618.

Chien CC, Fu WM, Huang HI et al. Expression of neurotrophic factors inneonatal rats after peripheral inflammation. J Pain 2007; 8(2): 161167.

Geng SJ, Liao FF, Dang WH et al. Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation. Exp Neurol 2010; 222(2):256-266.

Li L, Xian CJ, Zhong JH et al. Upregulation of brain derived neurotrophic factor in the sensory pathway by selective motor nerve injury in adult rats. Neurotox Res 2006; 9(4):269-283.

Wang X, Ratnam J, Zou B et al. TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain. J Neurosci 2009; 29(17):55085515.

Yajima Y, Narita M, Matsumoto N et al. Involvement of a spinal brain-derived neurotrophic factor/full length Trk B pathway in the development of nerve injury-induced thermal hyperalgesia in mice. Brain Res 2002; 958(2):338-346.

Minichiello L, Casagranda F, Tatche R et al. Point mutation in trk B causes loss of NT-4 dependent neurons without major effectson diverse BDNF responses. Neuron 1998; 21:335-345.

Boucher TJ, Okuse K, Bennett DL et al. Potent analgesic effects of GDNF in neuropathic pain states. Science 2000; 290(5489):124-7.


  • There are currently no refbacks.