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Pharmacological Management of Neuropathic Pain

  • Therapy In Practice
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Abstract

In health, the nervous system exists in a balance between inhibitory and excitatory influences. This balance may be upset if neural tissue is damaged or irritated and may give rise to neuropathic pain. Such neuropathic pain does not respond consistently to opioid analgesics or NSAIDs and it may therefore be necessary to utilise other therapeutic agents with known activity on either the excitatory or inhibitory components of the pain pathway. These other agents are traditionally considered with reference to their original uses; we still refer to tricyclic antidepressants (TCAs) and anticonvulsant drugs when a consideration of their modes of action may allow more rational use. For example, carbamazepine is related to the TCAs by virtue of its chemical structure and proposed mode of action and yet is still classified as an anticonvulsant drug.

With respect to the opioids, increasing evidence points to an analgesic effect in neuropathic pain, although concerns regarding tolerance and dependence still prevent more widespread use. The anticonvulsants comprise a group of compounds possessing anticonvulsant and analgesic properties, but each possesses differing modes of action and so several members of the class should be tried before a conclusion is reached that they, as a whole, are ineffective. TCAs may also have a role in the treatment of neuropathic pain. As with all drugs, if their use is not associated with pain relief in a defined period of time, their use should be terminated. Topical TCAs may also have a role where the area of neuropathic pain is small. Other options, such as SSRIs, membrane stabilisers, capsaicin, baclofen and clonidine may have potential in treating neuropathic pain.

The available evidence regarding the efficacy of currently available agents for the treatment of neuropathic pain is sparse. With the knowledge of achieving analgesia, according to the modes of actions of various agents it is hoped that the treatment of this difficult condition may be more logical and successful.

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References

  1. McCleane GJ. Intramuscular fosphenytoin reduces neuropathic pain: a randomized, double blind, placebo controlled, crossover study. Analgesia 1999; 4: 479–82

    CAS  Google Scholar 

  2. McCleane GJ. Intravenous fosphenytoin relieves chronic neuropathic pain: a double blind, placebo controlled, crossover trial. Analgesia 2000; 5: 45–8

    CAS  Google Scholar 

  3. Max MB, Byas-Smith MG, Gracely RH, et al. Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo. Clin Neuropharmacol 1995; 18: 360–8

    Article  PubMed  CAS  Google Scholar 

  4. Dellemijn PL, Vanneste JA. Randomised double-blind activeplacebo controlled crossover trial of intravenous fentanyl in neuropathic pain. Lancet 1997; 349: 753–8

    Article  PubMed  CAS  Google Scholar 

  5. Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991; 41: 1024–8

    Article  PubMed  CAS  Google Scholar 

  6. Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998; 50: 1837–41

    Article  PubMed  CAS  Google Scholar 

  7. Sindrup SH, Andersen G, Madsen C, et al. Tramadol relieves pain and allodynia in polyneuropathy: a randomised, doubleblind, controlled trial. Pain 1999; 83: 85–90

    Article  PubMed  CAS  Google Scholar 

  8. Sindrup SH, Madsen C, Brosen K, et al. The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels. Clin Pharmacol Ther 1999; 66: 636–41

    PubMed  CAS  Google Scholar 

  9. Harati Y, Gooch C, Swenson M, et al. Double-blind randomized trial of tramadol for the treatment of pain of diabetic neuropathy. Neurology 1998; 50: 1842–6

    Article  PubMed  CAS  Google Scholar 

  10. Bergouignan M. Cures heureuses de nevralgies faciales esentielles par le diphenyldantoinate de soude. Rev Laryngol Otol Rhinol (Bord) 1942; 63: 41

    Google Scholar 

  11. Lang DG, Wang CM, Cooper BR. Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells. J Pharmacol Exp Ther 1993; 266: 829–35

    PubMed  CAS  Google Scholar 

  12. Ambrosio AF, Soaras-de-Silva P, Carvalho CM, et al. Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, BIA 2-093, and BIA 2-024. Neurochem Res 2002; 27: 121–30

    Article  PubMed  CAS  Google Scholar 

  13. Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha delta 2 sub unit of a calcium channel. J Biol Chem 1996; 271: 5768–76

    Article  PubMed  CAS  Google Scholar 

  14. Luo ZD, Calcutt NA, Higuera ES, et al. Injury type specific calcium channel alpha delta 2 sub unit up regulation in rat neuropathic pain models correlates with anti allodynic effects of gabapentin. J Pharmacol Exp Ther 2002; 303: 1199–205

    Article  PubMed  CAS  Google Scholar 

  15. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance P facilitated K+ evoked release of [3H] glutamate from rat caudal trigeminal nucleus slices. Pain 2001; 93: 191–6

    Article  PubMed  CAS  Google Scholar 

  16. Cunningham MO, Jones RSG. The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vivo. Neuropharmacology 2000; 39: 2139–46

    Article  PubMed  CAS  Google Scholar 

  17. Lees G, Leach MJ. Studies on the mechanisms of action of the novel anticonvulsant lamotrigine (Lamictal) using primary neuroglial cultures from rat cortex. Brain Res 1993; 612:190–9

    Article  PubMed  CAS  Google Scholar 

  18. Majola MP, McFadden ML, Connolly C, et al. Factors influencing phenytoin: induced gingival enlargement. J Clin Periodontal 2000; 27: 506–12

    Article  CAS  Google Scholar 

  19. Olatunde Farombi E, Akinloye O, Akinmoladun CO, et al. Hepatic drug metabolising enzyme induction and serum triglyceride elevation in rats treated with chlordiazepoxide, griseofluvin, rifampacin and phenytoin. Clin Chim Acta 1999; 289: 1–10

    Article  Google Scholar 

  20. Chadda VS, Mathur MS. Double blind study of the effects of diphenylhydantoin sodium on diabetic neuropathy. J Assoc Physicians India 1978; 26: 403–6

    PubMed  CAS  Google Scholar 

  21. McCleane GJ. Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blind, placebo controlled, crossover study. Anesth Analg 1999; 89: 985–8

    PubMed  CAS  Google Scholar 

  22. Rao VK, Felman PD, Dibbeil DG. Extravasation injury to the hand by intravenous phenytoin. J Neurosurg 1988; 68: 967–9

    Article  PubMed  CAS  Google Scholar 

  23. Kilarski DJ, Buchanan C, Von Behren L. Soft tissue damage associated with intravenous phenytoin. N Engl J Med 1984; 311: 1186–7

    PubMed  CAS  Google Scholar 

  24. Cheshire WP. Fosphenytoin: an intravenous option for the management of acute trigeminal neuralgia crisis. J Pain Symptom Manage 2001; 21: 506–10

    Article  PubMed  CAS  Google Scholar 

  25. McCleane GJ. Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain 2002; 3: 156–8

    PubMed  Google Scholar 

  26. Blom S. Trigeminal neuralgia: its treatment with a new anticonvulsant drug (G32883). Lancet 1962; I: 839–40

    Article  Google Scholar 

  27. Campbell FG, Graham JG, Zilkha KJ. Clinical trial of carbazepine (Tegretol) in trigeminal neuralgia. J Neurol Neurosurg Psychiatry 1966; 29: 265–7

    Article  PubMed  CAS  Google Scholar 

  28. Taylor JC, Brauer S, Espir ML. Long term treatment of trigeminal neuralgia with carbamazepine. Postgrad Med J 1981; 57: 16–8

    Article  PubMed  CAS  Google Scholar 

  29. Rull JA, Quibrera R, Gonzalez-Millan H, et al. Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol): double blind crossover trial. Diabetologia 1969; 5: 215–8

    Article  PubMed  CAS  Google Scholar 

  30. Leijon G, Bovie J. Central post stroke pain: a controlled trial of amitriptyline and carbamazepine. Pain 1989; 36: 27–36

    Article  PubMed  CAS  Google Scholar 

  31. Killian JM, Fromm GH. Carbamazepine in the treatment of neuralgia: use and side effects. Arch Neurol 1968; 19: 129–36

    Article  PubMed  CAS  Google Scholar 

  32. Biton V. Effect of antiepileptic drugs on bodyweight: overview and clinical implications for the treatment of epilepsy. CNS Drugs 2003; 17: 781–91

    Article  PubMed  CAS  Google Scholar 

  33. Zakrzewska JM, Patsalos PN. Long-term cohort study comparing medical (oxcarbazepine) and surgical management of intractable trigeminal neuralgia. Pain 2002; 95: 259–66

    Article  PubMed  CAS  Google Scholar 

  34. Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 1998; 51: 611–4

    Article  PubMed  CAS  Google Scholar 

  35. Sist T, Filadora V, Miner M, et al. Gabapentin for idiopathic trigeminal neuralgia: report of two cases. Neurology 1997; 48: 1467–71

    Article  PubMed  CAS  Google Scholar 

  36. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998; 280: 1837–42

    Article  PubMed  CAS  Google Scholar 

  37. Segal AZ, Rordorf G. Gabapentin as a novel treatment for postherpetic neuralgia. Neurology 1996; 46: 1175–6

    Article  PubMed  CAS  Google Scholar 

  38. Morello CM, Leckband SG, Stoner CP, et al. Randomized double blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Arch Intern Med 1999; 159: 1931–7

    Article  PubMed  CAS  Google Scholar 

  39. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the treatment of painful neuropathy in patients with diabetes mellitus. JAMA 1998; 280: 1831–6

    Article  PubMed  CAS  Google Scholar 

  40. Samkoff LM, Daras M, Tuchman AJ, et al. Amelioration of refractory dysesthetic limb pain in multiple sclerosis by gabapentin. Neurology 1997; 49: 304–5

    Article  PubMed  CAS  Google Scholar 

  41. Bosnjak S, Jelic S, Susnjar S, et al. Gabapentin for relief of neuropathic pain related to anticancer treatment: a preliminary study. J Chemother 2002; 14: 214–9

    PubMed  CAS  Google Scholar 

  42. Serpell MG, Neuropathic Pain Study Group. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain 2002; 99: 557–66

    Article  PubMed  CAS  Google Scholar 

  43. Fischer JH, Barr AN, Rogers SL, et al. Lack of serious toxicity following gabapentin overdose. Neurology 1994; 44: 982–3

    Article  PubMed  CAS  Google Scholar 

  44. Norton JW. Gabapentin withdrawal syndrome. Clin Neuropharmacol 2001; 24: 245–6

    Article  PubMed  CAS  Google Scholar 

  45. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, et al. Lamotrigine (Lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain 1997; 73: 223–30

    Article  PubMed  CAS  Google Scholar 

  46. Lunardi G, Leandri M, Albano C, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 1997; 48: 1714–7

    Article  PubMed  CAS  Google Scholar 

  47. Canavero S, Bonicalzi V. Lamotrigine control of trigeminal neuralgia: an expanded study. J Neurol 1997; 244: 527–32

    Article  PubMed  CAS  Google Scholar 

  48. Simpson DM, Olney R, McArthur JC, et al. A placebo controlled trial of lamotrigine for painful HIV associated neuropathy. Neurology 2000; 54: 2115–9

    Article  PubMed  CAS  Google Scholar 

  49. Finnerup NB, Sindrup SH, Bach FW, et al. Lamotrigine in spinal cord injury pain: a randomized controlled trial. Pain 2002; 96: 375–83

    Article  PubMed  CAS  Google Scholar 

  50. Eisenberg E, Lurie Y, Braker C, et al. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology 2001; 57: 505–9

    Article  PubMed  CAS  Google Scholar 

  51. Vestergaard K, Andersen G, Gottrup H, et al. Lamotrigine for central post stroke pain: a randomized controlled trial. Neurology 2001; 56: 184–90

    Article  PubMed  CAS  Google Scholar 

  52. McCleane GJ. Lamotrigine in the management of neuropathic pain: a review of the literature. Clin J Pain 2000; 16: 321–6

    Article  PubMed  CAS  Google Scholar 

  53. Sandner-Kiesling A, Rumpold Seitlinger G, Dorn C, et al. Lamotrigine monotherapy for control of neuralgia after nerve section. Acta Anaesthesiol Scand 2002; 46: 1261–4

    Article  PubMed  CAS  Google Scholar 

  54. McCleane GJ. 200mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind placebo controlled trial. Pain 1999; 83: 105–7

    Article  PubMed  CAS  Google Scholar 

  55. Drewes AM, Andreason A, Poulsen LH. Valproate for treatment of chronic central pain after spinal cord injury: a double-blind cross-over study. Paraplegia 1994; 32: 565–9

    Article  PubMed  CAS  Google Scholar 

  56. Kochar DK, Jain A, Agarwal RP, et al. Sodium valproate in the management of painful neuropathy in type 2 diabetes: a randomized placebo controlled study. Acta Neurol Scand 2002; 106: 248–52

    Article  PubMed  CAS  Google Scholar 

  57. Soderpalm B. Anticonvulsants: aspects of their mechanisms of action. Eur J Pain 2002; 6 Suppl. A: 3–9

    Article  PubMed  CAS  Google Scholar 

  58. Gilron I, Booher SL, Rowan JS, et al. Topiramate in trigeminal neuralgia: a randomized, placebo-controlled multiple crossover pilot study. Clin Neuropharmacol 2001; 24: 109–12

    Article  PubMed  CAS  Google Scholar 

  59. Watson CP, Evans RJ, Reed K, et al. Amitriptyline versus placebo in postherpetic neuralgia. Neurology 1982; 32: 671–3

    Article  PubMed  CAS  Google Scholar 

  60. Bowsher D. Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline. Br J Gen Pract 1992; 42: 244–6

    PubMed  CAS  Google Scholar 

  61. Watson CPN, Chipman M, Reed K, et al. Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, doubleblind, crossover trial. Pain 1992; 48: 29–36

    Article  PubMed  CAS  Google Scholar 

  62. Watson CPN, Evans RJ. A comparative trial of amitriptyline and zimelidine in post-herpetic neuralgia. Pain 1985; 23: 387–94

    Article  PubMed  CAS  Google Scholar 

  63. Max MB, Schafer SC, Culnane M, et al. Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988; 38: 1427–32

    Article  PubMed  CAS  Google Scholar 

  64. Kvinesdal B, Molin J, Froland A, et al. Imipramine treatment of painful diabetic neuropathy. JAMA 1984; 251: 1727–30

    Article  PubMed  CAS  Google Scholar 

  65. Bromm B, Meier W, Scharein E. Imipramine reduces experimental pain. Pain 1986; 25: 245–57

    Article  PubMed  CAS  Google Scholar 

  66. Poulsen L, Arendt-Nielsen L, Brosen K, et al. The hypoalgesic effect of imipramine in different human experimental pain models. Pain 1995; 60: 287–93

    Article  PubMed  CAS  Google Scholar 

  67. Sindrup SH, Ejlertsen B, Froland A, et al. Imipramine treatment in diabetic neuropathy: relief of subjective symptoms without changes in peripheral and autonomic function. Eur J Clin Pharmacol 1989; 37: 151–3

    Article  PubMed  CAS  Google Scholar 

  68. Sindrup SH, Gram LF, Skjold T, et al. Concentration response relationship in imipramine treatment of diabetic neuropathy symptoms. Clin Pharmacol Ther 1990; 47: 509–15

    Article  PubMed  CAS  Google Scholar 

  69. Langohr HD, Stohr M, Petruch F. An open and double-blind crossover study on the efficacy of clomipramine (Anafranil) in patients with painful mono- and polyneuropathies. Eur Neurol 1982; 21: 309–17

    Article  PubMed  CAS  Google Scholar 

  70. Sindrup SH, Gram LF, Skjold T, et al.Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms: a double blind cross-over study. Br J Clin Pharmacol 1990; 30: 683–91

    Article  PubMed  CAS  Google Scholar 

  71. Max MB, Lynch AS, Moiré J, et al. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992; 326: 1250–6

    Article  PubMed  CAS  Google Scholar 

  72. Max MB, Kishore-Kumar R, Schafer SC, et al. Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Pain 1991; 45: 3–9

    Article  PubMed  CAS  Google Scholar 

  73. Kishore-Kumar R, Max MB, Schafer SC, et al. Desipramine relieves postherpetic neuralgia. Clin Pharmacol Ther 1990; 47: 305–12

    Article  PubMed  CAS  Google Scholar 

  74. Hameroff SR, Cork RC, Scherer K, et al. Doxepin effects on chronic pain, depression and plasma opioids. J Clin Psychiatry 1982; 43: 22–7

    PubMed  CAS  Google Scholar 

  75. Max MB, Culnane M, Schafer SC, et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987; 37: 589–96

    Article  PubMed  CAS  Google Scholar 

  76. Botney M, Fields HL. Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system. Ann Neurol 1983; 13: 160–4

    Article  PubMed  CAS  Google Scholar 

  77. Ansuategui M, Naharro L, Feria M. Noradrenergic and opioidergic influences on the antinociceptive effect of clomipramine in the formalin test in rats. Psychopharmacology 1989; 98: 93–6

    Article  PubMed  CAS  Google Scholar 

  78. Pancrazio JJ, Kamatchi GL, Roscoe AK, et al. Inhibition of neuronal Na+ channels by antidepressant drugs. J Pharmacol Exp Ther 1998; 284: 208–14

    PubMed  CAS  Google Scholar 

  79. Habuchi Y, Furukawa T, Tanaka H, et al. Block of Na+ channels by imipramine in guinea pig cardiac ventricular cells. J Pharmacol Exp Ther 1991; 258: 1072–81

    Google Scholar 

  80. Bou-Abboud E, Nattel S. Molecular mechanisms of the reversal of imipramine induced sodium channel blockade by alkalinization in human cardiac myocytes. Cardiovasc Res 1998; 38: 395–404

    Article  PubMed  CAS  Google Scholar 

  81. Deffois A, Fage D, Carter C. Inhibition of synaptosomal veratridine-induced sodium influx by antidepressants and neuroleptics used in chronic pain. Neurosci Lett 1996; 220: 117–20

    Article  PubMed  CAS  Google Scholar 

  82. Sawynok J, Reid AR, Esser MJ. Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine. Pain 1999; 80: 45–55

    Article  PubMed  CAS  Google Scholar 

  83. Heughan CE, Allen GV, Chase TD, et al. Peripheral amitriptyline suppresses formalin-induced fos expression in the rat spinal cord. Anesth Analg 2002; 94: 427–31

    PubMed  CAS  Google Scholar 

  84. Sawynok J, Esser MJ, Reid AR. Peripheral antinociceptive actions of desimipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain 1999; 82: 149–58

    Article  PubMed  CAS  Google Scholar 

  85. McCleane GJ. Topical application of doxepin hydrochloride can reduce the symptoms of complex regional pain syndrome. Injury 2002; 33: 88–9

    Article  PubMed  Google Scholar 

  86. McCleane GJ. Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study. Br J Clin Pharmacol 2000; 49: 574–9

    Article  PubMed  CAS  Google Scholar 

  87. McCleane GJ. Topical doxepin hydrochloride reduces neuropathic pain: a randomized, double-blind, placebo controlled study. Pain Clinic 1999; 12: 47–50

    Article  Google Scholar 

  88. Epstein JB, Truelove EL, Oien H, et al. Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy. Oral Oncol 2001; 37: 632–7

    Article  PubMed  CAS  Google Scholar 

  89. Mercadente S, Arcuri E, Tirelli W, et al. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo controlled, double blind crossover study. Tumori 2002; 88: 239–42

    Google Scholar 

  90. Buckley NA, McManus PR. Fatal toxicity of serotonergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002; 325: 1332–4

    Article  PubMed  Google Scholar 

  91. 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: 135–44

    Article  PubMed  CAS  Google Scholar 

  92. Sindrup SH, Bjerre U, Dejgaard A, et al. The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Clin Pharmacol Ther 1992; 52: 547–52

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  95. Chabal C, Jacobson L, Mariano A, et al. The use of oral mexiletine for the treatment of pain after peripheral nerve injury. Anesthesiology 1992; 76: 513–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  97. Galer BS, Rowbotham MC, Perander J, et al. 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  PubMed  CAS  Google Scholar 

  98. Galer BS, Jensen MP, Ma T, et al. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle controlled, 3 week efficacy study with use of the neuropathic pain scale. Clin J Pain 2002; 18: 297–301

    Article  PubMed  Google Scholar 

  99. Gordon RA. Intravenous novocaine for analgesia in burns. CMAJ 1943; 49: 478–81

    CAS  Google Scholar 

  100. Furukawa T, Koumi S, Sakakibara Y, et al. An analysis of lidocaine block of sodium current in isolated human atrial and ventricular myocytes. J Mol Cell Cardiol 1995; 27: 831–46

    Article  PubMed  CAS  Google Scholar 

  101. Catterall WA. Common modes of drug action on Na channels: local anesthetics, antiarrhythmics and anticonvulsants. TIPS 1987; 8: 57–65

    CAS  Google Scholar 

  102. Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992; 48: 261–8

    Article  PubMed  CAS  Google Scholar 

  103. Woolf CJ, Wisenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain 1985; 23: 361–74

    Article  PubMed  CAS  Google Scholar 

  104. Kastrup J, Petersen P, Dejgard A, et al. Intravenous lidocaine infusion-a new treatment of chronic painful diabetic neuropathy? Pain 1987; 28: 69–75

    Article  PubMed  CAS  Google Scholar 

  105. Kastrup J, Bach FW, Petersen P, et al. Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma. Clin J Pain 1989; 5: 239–44

    Article  PubMed  CAS  Google Scholar 

  106. Ackerman WE, Colclough GW, Juneja MM, et al. The management of oral mexiletine and intravenous lidocaine to treat chronic painful symmetrical distal diabetic neuropathy. J Ky Med Assoc 1991; 89: 500–1

    PubMed  Google Scholar 

  107. Baranowski AP, De Courcey J, Bonello E. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. J Pain Symptom Manage 1999; 17: 429–33

    Article  PubMed  CAS  Google Scholar 

  108. Attal N, Gaude V, Brasseur L, et al. Intravenous lidocaine in central pain: a double blind, placebo controlled, psycho physical study. Neurology 2000; 54: 564–74

    Article  PubMed  CAS  Google Scholar 

  109. Medrik-Goldberg T, Lifschitz D, Pud D, et al. Intravenous lidocaine, amantadine, and placebo in the treatment of sciatica: a double blind, randomized, controlled study. Reg Anesth Pain Med 1999; 24: 534–40

    Article  PubMed  CAS  Google Scholar 

  110. Turnbull A. Tincture of capsicum as a remedy for chilblains and toothache. Dublin Med Press 1850; 6: 95–6

    Google Scholar 

  111. Fitzgerald M. Capsaicin and sensory neurones. Pain 1983; 15: 109–30

    Article  PubMed  CAS  Google Scholar 

  112. Rains C, Bryson HM. Topical capsaicin: a review of its pharmacological properties and therapeutic potential in post herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995; 7: 317–28

    Article  PubMed  CAS  Google Scholar 

  113. Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989; 21: 265–70

    Article  PubMed  CAS  Google Scholar 

  114. Watson CPN, Tyler KL, Bickers D, et al. A randomized vehicle controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther 1993; 15: 510–26

    PubMed  CAS  Google Scholar 

  115. Watson CPN, Evans RJ, Watt VR. Post herpetic neuralgia and topical capsaicin. Pain 1988; 33: 333–40

    Article  PubMed  CAS  Google Scholar 

  116. Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992; 15: 159–65

    Article  Google Scholar 

  117. Chad DA, Aronin N, Lundstrom R, et al. Does capsaicin relieve the pain of diabetic neuropathy? Pain 1990; 42: 387–8

    Article  PubMed  CAS  Google Scholar 

  118. The Capsaicin Study Group. Treatment of painful diabetic neuropathy with topical capsaicin. Arch Intern Med 1991; 151: 2225–9

    Article  Google Scholar 

  119. Tandan R, Lewis GA, Krusinski PB, et al. Topical capsaicin in painful diabetic neuropathy. Diabetes Care 1992; 15: 8–13

    Article  PubMed  CAS  Google Scholar 

  120. Scheffler NM, Sheital PL, Lipton MN. Treatment of painful diabetic neuropathy with capsaicin. J Am Podiatr Med Assoc 1991; 31: 288–93

    Google Scholar 

  121. Low PA, Opfer-Gehrking TL, Dyck PJ, et al. Double blind, placebo controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy. Pain 1995; 450: 163–8

    Article  Google Scholar 

  122. Ellison N, Loprinzi CL, Kugler J, et al. Phase III placebo controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol 1997; 15: 2974–80

    PubMed  CAS  Google Scholar 

  123. Watson CP, Evans RJ. The post-mastectomy pain syndrome and topical capsaicin: a randomised trial. Pain 1992; 51: 375–9

    Article  PubMed  CAS  Google Scholar 

  124. Yosipovitch G, Mailbach HI, Rowbotham MC. Effect of EMLA pre-treatment on capsaicin-induced burning and hyperalgesia. Acta Derm Venereol 1999; 79: 118–21

    Article  PubMed  CAS  Google Scholar 

  125. McCleane GJ, McLaughlin M. The addition of GTN to capsaicin cream reduces the discomfort associated with application of capsaicin alone: a volunteer study. Pain 1998; 78: 149–51

    Article  PubMed  CAS  Google Scholar 

  126. Walker RA, McCleane GJ. The addition of glyceryltrinitrate to capsaicin cream reduces the thermal allodynia associated with the use of capsaicin alone in humans. Neurosci Lett 2002; 332: 210–2

    Article  Google Scholar 

  127. McCleane GJ. The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study. Eur J Pain 2000; 4: 355–60

    Article  PubMed  CAS  Google Scholar 

  128. Fromm GH, Terrence CF, Chatta AS. Baclofen in the treatment of trigeminal neuralgia: double blind study and long term follow up. Ann Neurol 1984; 15: 240–4

    Article  PubMed  CAS  Google Scholar 

  129. Epstein JB, Grushka M, Le N. Topical clonidine for orofacial pain: a pilot study. J Orofac Pain 1997; 11(4): 346–52

    PubMed  CAS  Google Scholar 

  130. Byas-Smith MG, Max MB, Muir J, et al. Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two stage ‘enriched enrollment’ design. Pain 1995; 60: 267–74

    Article  PubMed  CAS  Google Scholar 

  131. Davis KD, Treede RD, Raja SN, et al. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain 1991; 47: 309–17

    Article  PubMed  CAS  Google Scholar 

  132. Zeigler D, Lynch SA, Muir J, et al. Transdermal clonidine versus placebo in painful diabetic neuropathy. Pain 1992; 48: 403–8

    Article  PubMed  CAS  Google Scholar 

  133. Nakamura M, Ferreira SH. Peripheral analgesic action of clonidine: mediated by release of endogenous enkephalin-like substances. Eur J Pharmacol 1988; 146: 223–8

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The author has no known conflicts of interest that are directly relevant to the content of this review or the preparations it mentions.

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  1. Rampark Pain Centre, 2 Rampark, Dromore Road, Lurgan, BT66 7JH, N. Ireland, UK

    Gary McCleane

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McCleane, G. Pharmacological Management of Neuropathic Pain. CNS Drugs 17, 1031–1043 (2003). https://doi.org/10.2165/00023210-200317140-00003

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