Drugs

, Volume 60, Issue 5, pp 1029–1052 | Cite as

Anticonvulsants for Neuropathic Pain Syndromes

Mechanisms of Action and Place in Therapy
  • Ivo W. Tremont-Lukats
  • Carla Megeff
  • Misha-Miroslav Backonja
Review Article

Abstract

Neuropathic pain, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human models of neuropathic pain has shown that a number of pathophysiological and biochemical changes take place in the nervous system as a result of an insult. This property of the nervous system to adapt morphologically and functionally to external stimuli is known as neuroplasticity and plays a crucial role in the onset and maintenance of pain symptoms. Many similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders.

Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic neuralgia.

The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapentin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain.

Evidence for the efficacy of phenytoin as an antinociceptive agent is, at best, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although another randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have antihyperalgesic and antinociceptive activities based on result in animal models of neuropathic pain, but the efficacy of these drugs in the treatment of human neuropathic pain has not yet been fully determined in clinical trials.

The role of anticonvulsant drugs in the treatment of neuropathic pain is evolving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropathic pain syndromes and well-designed clinical trials should further the opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.

References

  1. 1.
    Mitchell SW, Morehouse GR, Keen WW. Gunshot wounds and other injuries of nerves. oPhiladelphia: JB Lippincott & Co., 1864Google Scholar
  2. 2.
    Bennett GJ, Xie YK. A peripheral mononeuropathy in the rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87–107PubMedCrossRefGoogle Scholar
  3. 3.
    Casey K. Pain and central nervous system disease: a summary and overview. In: Casey K, editor. Pain and central nervous system disease: central pain syndromes. New York: Raven Press, 1991: 1–11Google Scholar
  4. 4.
    Wall PD, Gutnick M. Properties of afferent nerve impulses originating from a neuroma. Nature 1974; 248: 740–3PubMedCrossRefGoogle Scholar
  5. 5.
    Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990; 43: 205–18PubMedCrossRefGoogle Scholar
  6. 6.
    Chung K, Lee BH, Yoon YW, et al. Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model. J Comp Neurol 1996; 376: 241–52PubMedCrossRefGoogle Scholar
  7. 7.
    DeLeo JA, Coombs DW, Willenbring S, et al. Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat. Pain 1994; 56: 9–16PubMedCrossRefGoogle Scholar
  8. 8.
    Maves TJ, Pechman PS, Gebhart PS, et al. Possible chemical contribution from chronic gut sutures produces disorders of pain sensation like those seen in man. Pain 1993; 54: 57–69PubMedCrossRefGoogle Scholar
  9. 9.
    LaMotte RH, Lundberg LE, Todjebork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 1992; 448: 749–64PubMedGoogle Scholar
  10. 10.
    Bennett G. An animal model of neuropathic pain: a review. Muscle Nerve 1993; 16: 1040–8PubMedCrossRefGoogle Scholar
  11. 11.
    Dickenson A. Spinal cord pharmacology of pain. Br J Anaesth 1995; 75: 193–200PubMedCrossRefGoogle Scholar
  12. 12.
    Neumann S, Doubell TP, Leslie T, et al. Inflammatory pain sensitivity mediated by phenotypic switch in myelinated primary senory neurons. Nature 1996; 384: 360–4PubMedCrossRefGoogle Scholar
  13. 13.
    Coderre TJ, Melzack R. The contribution of excitatory aminoacids to central sensitization and persistent nociception after formalin-induced tissue injury. J Neurosci 1992; 12: 3665–70PubMedGoogle Scholar
  14. 14.
    Jett MF, McGuirk J, Waligora D, et al. The effects of mexiletine, desipramine and fluoxetine in rat models involving central sensitization. Pain 1997; 69: 161–9PubMedCrossRefGoogle Scholar
  15. 15.
    Kolzenburg M, Torebjork HE, Wahren LK. Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neurogenic pain. Brain 1994; 117: 579–91CrossRefGoogle Scholar
  16. 16.
    Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991; 44: 293–9PubMedCrossRefGoogle Scholar
  17. 17.
    Ochoa JL, Yarnitsky D. Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993; 33: 465–72PubMedCrossRefGoogle Scholar
  18. 18.
    Gottrup H, Nielsen J, Arendt-Nielsen L, et al. The relationship between sensor thresholds and mechanical hyperalgesia in nerve injury. Pain 1998; 75: 321–9PubMedCrossRefGoogle Scholar
  19. 19.
    Kolzenburg M, Lundberg LE, Torebjork HE. Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain 1992; 51: 207–19CrossRefGoogle Scholar
  20. 20.
    Cline MA, Ochoa J, Torebjork HE. Chronic hyperalgesia and skin wanning caused by sensitized C nociceptors. Brain 1989; 112: 621–47PubMedCrossRefGoogle Scholar
  21. 21.
    LaMotte RH, Thalhammer JG, Torebjork HE, et al. Peripheral neural mechanisms of cutaneous hyperalgesia following mild injury by heat. J Neurosci 1982; 2: 765–81PubMedGoogle Scholar
  22. 22.
    Coderre TJ, Melzack R. Cutaneous hyperalgesia: contributions of the peripheral and central nervous system to the increase in pain sensitivity after injury. Brain Res 1987; 404: 95–106PubMedCrossRefGoogle Scholar
  23. 23.
    Craig AD, Bushnell MC. The thermal grill illusion: unmasking the burn of cold pain. Science 1994; 265: 252–5PubMedCrossRefGoogle Scholar
  24. 24.
    Thomas R. Excitatory amino acids in health and disease. J Am Geriatr Soc 1995; 43: 1279–89PubMedGoogle Scholar
  25. 25.
    McNamara J. Drugs acting on the central nervous system. In: Harman G, Limbird LE, Morinoff PB, et al., editors. Goodman’s and Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 461–86Google Scholar
  26. 26.
    Sotah M, Foong FW. A mechanism of carbamazepine analgesia as shown by bradykinin-induced trigeminal pain. Brain Res Bull 1983; 10: 407–9CrossRefGoogle Scholar
  27. 27.
    Burchiel K. carbamazepine inhibits spontaneous activity in experimental neuromas. Exp Neurol 1988; 102: 249–53PubMedCrossRefGoogle Scholar
  28. 28.
    Chapman V, Suzuki R, Chamarette HL, et al. Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats. Pain 1998; 75: 261–72PubMedCrossRefGoogle Scholar
  29. 29.
    Tanelian DL, Cousins MJ. Combined neurogenic and nociceptive pain in a patient with Pancoast tumor managed by epidural hydromorphone and oral carbamazepine. Pain 1989; 36: 85–8PubMedCrossRefGoogle Scholar
  30. 30.
    Tanelian DL, Maclver MB. Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury. Anesthesiology 1991; 74: 934–6PubMedCrossRefGoogle Scholar
  31. 31.
    Blorn S. Trigeminal neuralgia: its treatment with a new anticonvulsant drug. Lancet 1962; I: 839–40Google Scholar
  32. 32.
    Blom S. Tic douloureoux treated with new anticonvulsants. Arch Neurol 1963; 9: 285–90PubMedCrossRefGoogle Scholar
  33. 33.
    Campbell FG, Graham JG, Zikha KJ. Clinical trial of carbamazepine (Tegretol) in trigeminal neuralgia. J Neurosurg Neurol Psychiatry 1966; 29: 265–7CrossRefGoogle Scholar
  34. 34.
    Killian JM, Fromm GH. Carbamazepine in the treatment of neuralgia. Arch Neurol 1968; 19: 129–36PubMedCrossRefGoogle Scholar
  35. 35.
    Rull JA, Quibrera R, González-Millan H, et al. Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine: double-blind crossover study. Diabetologia 1969; 5: 215–20PubMedCrossRefGoogle Scholar
  36. 36.
    Nicol C. A four year double blind randomized study of tegretol in facial pain. Headache 1969; 9: 54–7PubMedCrossRefGoogle Scholar
  37. 37.
    Wilton T. Tegretol in the treatment of diabetic neuropathy. S Afr Med J 1974; 27: 869–72Google Scholar
  38. 38.
    Vilming ST, Lyberg T, Lataste X. Tizanidine in the management of trigeminal neuralgia. Cephalalgia 1986; 6: 181–2PubMedCrossRefGoogle Scholar
  39. 39.
    Lindstrom P, Lindblom U. The analgesic effect of tocainide in trigeminal neuralgia. Pain 1987; 28: 45–50PubMedCrossRefGoogle Scholar
  40. 40.
    Lechin F, van der Dijs B, Lechin ME, et al. Pimozide therapy for trigeminal neuralgia. Arch Neurol 1989; 46: 960–3PubMedCrossRefGoogle Scholar
  41. 41.
    Leijon G, Boivie J. Central post-stroke pain: a controlled trial of amitriptyline and carbamazepine. Pain 1989; 36: 27–36PubMedCrossRefGoogle Scholar
  42. 42.
    Gomez-Perez FJ, Choza R, Ríos JM, et al. Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy. Arch Med Res 1996; 27: 525–9Google Scholar
  43. 43.
    Saudek CD, Werns S, Reidenberg MM. Phenytoin in the treatment of diabetic symmetrical polyneuropathy. Clin Pharmacol Ther 1977; 22: 196–9PubMedGoogle Scholar
  44. 44.
    Chadda VS, Mathur MS. Double blind study of the effects of dyphenylhidantoin sodium in diabetic neuropathy. J Assoc Phys India 1978; 26: 403–6Google Scholar
  45. 45.
    Yajnik S, Singh GP, Singh G, et al. Phenytoin as a coanalgesic in cancer pain. J Pain Symptom Manage 1992; 7: 209–13PubMedCrossRefGoogle Scholar
  46. 46.
    McCleane GJ. Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study. Anesth Analg 1999; 89: 985–8PubMedGoogle Scholar
  47. 47.
    Max MB, Schafer SC, Culnane M, et al. Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988; 38: 1427–32PubMedCrossRefGoogle Scholar
  48. 48.
    Drewes AM, Andreasen A, Poulsen LH. Valproate for treatment of chronic central pain after spinal cord injury: a double-blind cross-over study. Paraplegia 1994; 32: 565–9PubMedCrossRefGoogle Scholar
  49. 49.
    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: 223–30PubMedCrossRefGoogle Scholar
  50. 50.
    Simpson DM, Olney R, McArthur JC, et al. A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy. Neurology 2000; 54: 2115–19PubMedCrossRefGoogle Scholar
  51. 51.
    McCleane G. 200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial. Pain 1999; 83: 105–7PubMedCrossRefGoogle Scholar
  52. 52.
    Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA 1998; 280: 1831–6PubMedCrossRefGoogle Scholar
  53. 53.
    Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of post-herpetic neuralgia: a randomized controlled trial. JAMA 1998; 280: 1837–42PubMedCrossRefGoogle Scholar
  54. 54.
    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: 1931–7PubMedCrossRefGoogle Scholar
  55. 55.
    Webb J, Kamali F. Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers. Pain 1998; 76: 357–63PubMedCrossRefGoogle Scholar
  56. 56.
    Rockliff BW, Davis EH. Controlled sequential trials of carbamazepine in trigeminal neuralgia. Arch Neurol 1966; 15: 129–36PubMedCrossRefGoogle Scholar
  57. 57.
    Gerson GR, Jones RB, Luscombe DK. Studies on the concomitant use of carbamazepine and clomipramine for the relief of post-herpetic neuralgia. Postgrad Med J 1977; 53: 104–9PubMedGoogle Scholar
  58. 58.
    Spillane J. The treatment of trigeminal neuralgia. Practitioner 1964; 192: 71–7PubMedGoogle Scholar
  59. 59.
    Raskin NH, Levinson SA, Hoffman PM, et al. Postsympathectomy neuralgia: amelioration with diphenylhidantoin and carbamazepine. Am J Surg 1974; 128: 75–8PubMedCrossRefGoogle Scholar
  60. 60.
    Chakrabarti AK, Sawantaray SK. Diabetic peripheral neuropathy: nerve conduction studies before, during, and after carbamazepine therapy. Aust N Z J Med 1976; 6: 565–8PubMedCrossRefGoogle Scholar
  61. 61.
    Tomson T, Tybring G, Bertilsson L. carbamazepine therapy in trigeminal neuralgia: clinical effects in relation to plasma concentration. Arch Neurol 1980; 37: 699–703PubMedCrossRefGoogle Scholar
  62. 62.
    Taylor J, Espir ML, Brauer S. Long-term treatment of trigeminal neuralgia with carbamazepine. Postgrad Med J 1981; 57: 16–8PubMedCrossRefGoogle Scholar
  63. 63.
    Peiris JB, Perera GLS, Dvendra SV, et al. Sodium valproate in trigeminal neuralgia. Med J Aust 1980; 2: 278–9PubMedGoogle Scholar
  64. 64.
    Swerdlow M, Cundill JG. Anticonvulsant drugs in the treatment of lancinating pain: a comparison. Anaesthesia 1981; 36: 1129–32PubMedCrossRefGoogle Scholar
  65. 65.
    Caccia M. Clonazepam in facial neuralgia and cluster headache: clinical and electrophysiological study. Eur Neurol 1975; 13: 560–3PubMedCrossRefGoogle Scholar
  66. 66.
    Court JE, Kase CS. Treatment of tic douloureux with a new anticonvulsant (Clonazepam). J Neurol Neurosurg Psychiatry 1976; 39: 297–9PubMedCrossRefGoogle Scholar
  67. 67.
    Smirne S, Scarlato G. Clonazepam in cranial neuralgias. Med J Aust 1977; 1: 93–4PubMedGoogle Scholar
  68. 68.
    Bouckhoms AJ, Litman RE. Clonazepam in the treatment of neuralgic pain syndrome. Psychosomatics 1985; 26: 933–6CrossRefGoogle Scholar
  69. 69.
    Rosenberg JM, Harrell C, Ristic H, et al. The effect of gabapentin on neuropathic pain. Clin J Pain 1997; 13: 251–5PubMedCrossRefGoogle Scholar
  70. 70.
    Attal N, Brasseur L, Parker F, et al. Effects of gabapentin on different components of peripheral and central neuropathic pain syndromes: a pilot study. Eur Neurol 1998; 40: 191–200PubMedCrossRefGoogle Scholar
  71. 71.
    Solaro C, Lunardi GL, Capello E, et al. An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology 1998; 51: 609–11PubMedCrossRefGoogle Scholar
  72. 72.
    Canavero S, Bonicalzi V. Lamotrigine control of trigeminal neuralgia. J Neurol 1997; 244: 527–32PubMedCrossRefGoogle Scholar
  73. 73.
    Lunardi GL, Leandri M, Albano C, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 1997; 48: 1714–7PubMedCrossRefGoogle Scholar
  74. 74.
    Eisenberg E, Alon N, Ishay A, et al. Lamotrigine in the treatment of painful diabetic neuropathy. Eur J Neurol 1998; 5: 167–73PubMedCrossRefGoogle Scholar
  75. 75.
    Cianchetti C, Zuddas A, Randazzo AP, et al. Lamotrigine adjunctive therapy in painful phenomena in MS: preliminary observations [abstract]. Neurology 1999; 53: 433PubMedCrossRefGoogle Scholar
  76. 76.
    Potter D, Edwards KR, Bennington VT. Potential role of topiramate in relief of neuropathic pain [abstract]. Neurology 1998; 50: A255Google Scholar
  77. 77.
    Woodforde JM, Dwyer B, McEwen B. Treatment of post-herpetic neuralgia. Med J Aust 1965; 1: 869–72Google Scholar
  78. 78.
    Carasso RL, Yehuda S, Streifler M. Clomipramine and amitriptyline in the treatment of severe pain. Int J Neuroscience 1979; 9: 191–4CrossRefGoogle Scholar
  79. 79.
    Watson CP, Evans RJ, Reed K. Amitriptyline versus placebo in pos herpetic neuralgia. Neurology 1982; 32: 671–3PubMedCrossRefGoogle Scholar
  80. 80.
    Watson CP, Evans RJ. A comparative trial of amitriptyline and simelidine in post herpetic neuralgia. Pain 1985; 23: 387–94PubMedCrossRefGoogle Scholar
  81. 81.
    Facchetti D, Chiroli S, Bascelli C, et al. Gabapentin (GBP) versus carbamazepine in conservative treatment of carpal tunnel syndrome [abstract]. Neurology 1999; 52: A203Google Scholar
  82. 82.
    Bergouignan M. Cures heureuses de nevralgies faciales essentielles par diphenyl-hidantoinate de soude. Rev Laryngol Otol Rhinol 1942; 63: 34–41Google Scholar
  83. 83.
    Swerdlow M. Anticonvulsant drugs and chronic pain. Clin Neuropharmacol 1984; 7: 51–82PubMedCrossRefGoogle Scholar
  84. 84.
    Yaari Y, Devor M. Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas. Neurosci Lett 1985; 58: 117–22PubMedCrossRefGoogle Scholar
  85. 85.
    Duckrow RB, Taub A. The effect of diphenylhydantoin on self-mutilation in rats produced by unilateral multiple dorsal rhizotomy. Exp Neurol 1977; 54: 33–41PubMedCrossRefGoogle Scholar
  86. 86.
    Hunter JC, Gogas KR, Hedley LR, et al. The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 1997; 324: 153–60PubMedCrossRefGoogle Scholar
  87. 87.
    McQuay H, Carroll D, Jadad A, et al. Anticonvulsant drugs for management of pain: a systematic review. BMJ 1995; 311: 1047–52PubMedCrossRefGoogle Scholar
  88. 88.
    Ellenberg M. Treatment of diabetic neuropathy with diphenylhidantoin. N Y State J Med 1968; 68: 2653–6PubMedGoogle Scholar
  89. 89.
    Dallocchio C, Buffa C, Mazzarello P, et al. Gabapentin versus amitriptyline in painful diabetic neuropathy in the elderly. Neurology 1998; 50: A102–3Google Scholar
  90. 90.
    Savitskaya O. Comparative effectiveness of anti-epileptic preparations in treatment of patients with neuralgia of the trigeminal nerve. Zh Nevropatol Psikhiatr Im S S Korsakova 1980; 80: 530–5Google Scholar
  91. 91.
    Taylor J. Trigeminal neuralgia treated with G 32.883. J Neurol Neurosurg Psychiatry 1963; 26: 553–4Google Scholar
  92. 92.
    Braunhofer J, Zikha L. Eroffnet Tegretal neue Therapiemoglichkeiten bei bestimmten neurologischen und endokrinen Krankheitsbildern? Eine klinische elektroenzephalographische und dunnschichtchromatographische Studie. Med Welt 1966; 36: 1875–80PubMedGoogle Scholar
  93. 93.
    Dalessio DJ, Abbott K. A new agent in the treatment of tic douloureoux. Headache 1966; 5: 103–7PubMedCrossRefGoogle Scholar
  94. 94.
    Javid M, Dardenne G. Evaluation of carbamazepine in the management of tic douloureux and other painful disorders. Wis Med J 1969; 68: 95–101PubMedGoogle Scholar
  95. 95.
    Rasmussen P, Riishede J. Facial pain treated with carbamazepine (Tegretol). Acta Neurol Scand 1970; 46: 385–408PubMedCrossRefGoogle Scholar
  96. 96.
    Lemoyne J. Le traitement de la névralgie faciale essentielle par le dimethyl-dithio-hydantoine. Concours Med 1951; 73: 461–3PubMedGoogle Scholar
  97. 97.
    Jensen H. Die Behandlung der Trigeminusneuralgie mit Diphenylhidantoin. Arztl Wschr 1954; 9: 105–8Google Scholar
  98. 98.
    Braham I, Saia A. Phenytoin in the treatment of trigeminal and other neuralgias. Lancet 1960; II: 892–3CrossRefGoogle Scholar
  99. 99.
    Cheshire W. Felbamate relieved trigeminal neuralgia. Clin J Pain 1995; 11: 139–42PubMedCrossRefGoogle Scholar
  100. 100.
    Valzania F, Strafella A, Nassetti SA, et al. Gabapentin in idiopathic trigeminal neuralgia [abstract]. Neurology 1998; 50: A379Google Scholar
  101. 101.
    La Spina I, Porazzi D, Maggiolo F, et al. Gabapentin (GBP) in painful AIDS-related neuropathy [abstract]. Neurology 1999; 52: A190CrossRefGoogle Scholar
  102. 102.
    Gatti A, Stefano J, Beretta S, et al. Gabapentin in the treatment of distal symmetric axonopathy in HIV infected patients [abstract]. Neurology 1998; 50: A216Google Scholar
  103. 103.
    Elliott F, Little A, Milbrandt W. Carbamazepine for phantomlimb phenomena [abstract]. N Engl J Med 1976; 295: 678PubMedGoogle Scholar
  104. 104.
    Harbison J, Dennehy F, Keating D. Lamotrigine for pain with hyperalgesia. Irish Med J 1997; 90: 56Google Scholar
  105. 105.
    Bartusch SL, Sanders BJ, D’Alessio JG, et al. Clonazepam for the treatment of lancinating phantom limb pain. Clin J Pain 1996; 12: 59–62PubMedCrossRefGoogle Scholar
  106. 106.
    Esmir ML, Millac P. Treatment of paroxysmal disorders in multiple sclerosis with carbamazepine (Tegretol). J Neurol Neurosurg Psychiatry 1970; 33: 528–31CrossRefGoogle Scholar
  107. 107.
    Shibasaki H, Kuroiwa Y. Painful tonic seizure in multiple sclerosis. Arch Neurol 1974; 30: 47–51PubMedCrossRefGoogle Scholar
  108. 108.
    Khan O. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 1998; 51: 611–4PubMedCrossRefGoogle Scholar
  109. 109.
    McCleane G. Lamotrigine can reduce neurogenic pain associated with multiple sclerosis. Clin J Pain 1998; 14: 269–70PubMedCrossRefGoogle Scholar
  110. 110.
    Chaturvedi S. Phenytoin in reflex sympathetic dystrophy. Pain 1989; 36: 379–80PubMedCrossRefGoogle Scholar
  111. 111.
    Mellick GA, Mellick LB. Gabapentin in the management of reflex sympathetic dystrophy. JPain Symptom Manage 1995; 10: 265–6CrossRefGoogle Scholar
  112. 112.
    Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain 1996; 12: 56–8PubMedCrossRefGoogle Scholar
  113. 113.
    Sist TC, Filadora VA, Miner M, et al. Experience with gabapentin for neuroapthic pain in the head and neck: report of ten cases. Reg Anesth 1997; 22: 473–8PubMedCrossRefGoogle Scholar
  114. 114.
    Merren M. Gabapentin for treatment of pain and tremor. South Med J 1998; 91: 739–44PubMedCrossRefGoogle Scholar
  115. 115.
    Caraceni A, Zecca E, Martini C, et al. Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain. J Pain Symptom Manage 1999; 17: 441–5PubMedCrossRefGoogle Scholar
  116. 116.
    Gibson JC, White LC. Denervation hyperpathia: a convulsive syndrome of the spinal cord responsive to carbamazepine therapy [letter]. J Neurosurg 1971; 35: 287PubMedCrossRefGoogle Scholar
  117. 117.
    Fine W. Post hemiplegic epilepsy in the elderly. BMJ 1967; 1(534): 199–201PubMedCrossRefGoogle Scholar
  118. 118.
    Cantor F. Phenytoin treatment of thalamic pain [letter]. BMJ 1972; 2: 590CrossRefGoogle Scholar
  119. 119.
    Agnew DA, Goldberg VD. A brief trial of phenytoin for thalamic pain. Bull Los Angeles Neurol Soc 1976; 41: 9–12PubMedGoogle Scholar
  120. 120.
    Allen R. Neuropathic pain in the cancer patient. Neurol Clin North Am 1998; 16: 869–7Google Scholar
  121. 121.
    Sawynok J. GABAergic mechanisms of analgesia: an update. Pharmacol Biochem Behav 1987; 26: 463–74PubMedCrossRefGoogle Scholar
  122. 122.
    Yasuda T, Iwamoto T, Ohara M, et al. The novel analgesic compound OT-7100 attenuates mechanical nociceptive responses in animal models of acute and peripheral neuropathic hyperalgesia. Jap J Pharmacol 1999; 79: 65–73PubMedCrossRefGoogle Scholar
  123. 123.
    Bouckoms A. Intravenous lorazepam for pain relief of intractable neuralgia. Pain 1987; Suppl. 4: S347Google Scholar
  124. 124.
    Ko GY, Brown-Croyts LM, Teyler T. The effects of anticonvulsant drugs on NMDA-EPSP, AMPA-EPSP, and GABA-IPSP in the rat hippoccampus. Brain Res Bull 1997; 42: 297–302PubMedCrossRefGoogle Scholar
  125. 125.
    Shuto K, Nishiyaki T. Sodium dipropylacetate. Pharmacometrics 1970; 4: 937–49Google Scholar
  126. 126.
    Mesdjian E, DeFeudis FV, Valli M, et al. Antinociceptive action of sodium valproate in the mouse. Gen Pharmacol 1983; 14: 697–9PubMedCrossRefGoogle Scholar
  127. 127.
    Abulaban FS, Dhariwal MAH, Al-Bekairi AM, et al. Anti-nociceptive activity of sodium valproate in mice after chronic treatment. Gen Pharmacol 1997; 29: 463–7PubMedCrossRefGoogle Scholar
  128. 128.
    Lee WS, Limmroth V, Ayala C, et al. Peripheral GABA-A receptor-mediated effects of sodium valproate on durai plasma protein extravasation to subsance P and trigeminal stimulation. Br J Pharmacol 1995; 116: 1661–7PubMedCrossRefGoogle Scholar
  129. 129.
    Cutrer FM, Moskowitz MA. The actions of valproate and neurosteroids in a model of trigeminal pain. Headache 1996; 36: 579–85PubMedCrossRefGoogle Scholar
  130. 130.
    Alley KO, Kulkarni SK. GABAergic agents-induced anti-nociceptive effect in mice. Methods Find Exp Clin Pharmacol 1989; 11: 597–601Google Scholar
  131. 131.
    Raftery H. The management of post herpetic pain using sodium valproate and amitriptyline. Irish Med J 1979; 72: 399–401Google Scholar
  132. 132.
    Bowsher D, Lahuerta J, Nelson A. A case of tabes dorsalis with tonic pupils and lightning pains relieved by sodium valproate. J Neurol Neurosurg Psychiatry 1987; 50: 239–41PubMedCrossRefGoogle Scholar
  133. 133.
    Leach MJ, Marden CM, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug. II. Neurochemical studies on the mechanism of action. Epilepsia 1986; 27: 490–7Google Scholar
  134. 134.
    Nakamura-Craig M, Folienfant R. Analgesic reffects of lamotrigine in an experimental model of neuropathic pain in rats [abstract]. Br J Pharmacol 1992; 107: 337PGoogle Scholar
  135. 135.
    Nakamura-Craig M, Folienfant R. Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and in the chronic hyperalgesia in rats with streptozotocin-induced diabetes. Pain 1995; 63: 33–7PubMedCrossRefGoogle Scholar
  136. 136.
    Klamt J. Effects of intrathecally administered lamotrigine, a glutamate release inhibitor, on short- and long-term models of hyperalgesia in rats. Anesthesiology 1998; 88: 487–94PubMedCrossRefGoogle Scholar
  137. 137.
    Kukushkin ML, Danilova EI, Grafova VN, et al. Effect of lamotrigine on the development of neurogenic pain syndrome in rats. Bull Exp Biol Med 1998; 125: 517–21CrossRefGoogle Scholar
  138. 138.
    Taylor CP, Gee NS, Su T-Z, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998; 29: 233–49PubMedCrossRefGoogle Scholar
  139. 139.
    Field MJ, McCleary S, Hughes J, et al. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat. Pain 1999; 80: 391–8PubMedCrossRefGoogle Scholar
  140. 140.
    Abdi S, Lee DH, JM. C. The anti-allodynic effects of amytriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain. Anesth Analg 1998; 87: 1360–6PubMedGoogle Scholar
  141. 141.
    Pan H-L, Eisenach JC, Chung JM. Gabapentin suppresses ectopic nerve discharges. J Pharmacol Exp Ther 1999; 288: 1026–30PubMedGoogle Scholar
  142. 142.
    Gillin S, Sorkin LS. Gabapentin reverses the allodynia produced by the administration of anti-GD2 ganglioside, and immuno-therapeutic drug. Anesth Analg 1998; 86: 111–6PubMedGoogle Scholar
  143. 143.
    Petroff OA, Rothman DL, Behar KL, et al. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol 1996; 39: 95–9PubMedCrossRefGoogle Scholar
  144. 144.
    Mancardi G, Messmer Uccelli M, Murialdo A, et al. Gabapentin is effective in treating nocturnal painful spasms in muktiple sclerosis [abstract]. Neurology 1999; 52: A134Google Scholar
  145. 145.
    Vinik A, Fonseca V, Lamoeaux L, et al. Neurontin (Gabapentin, GBP) improves quality of life (QOL) in patients with painful diabetic peripheral neuropathy [abstract]. Diabetes 1998; 46: A374Google Scholar
  146. 146.
    Gorson KC, Schott C, Rand WM, et al. Gabapentin in the treatment of painful diabetic neuropathy: a placebo-controlled, double-blind, crossover trial [abstract]. Neurology 1998; 50: A103CrossRefGoogle Scholar
  147. 147.
    Morello CM, Leckbrand SG, Stoner CP. Effect of gabapentin compared to amitriptyline on pain in diabetic peripheral neuropathy [abstract]. Diabetes 1998; 47: A134CrossRefGoogle Scholar
  148. 148.
    Edwards K, Glantz MJ, Button J, et al. Efficacy and safety of topiramate in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study [abstract S15.001]. Neurology 2000; 54S3: A81Google Scholar
  149. 149.
    Iacobellis D, Allen R, Lamoreaux L, et al. A double-blind, placebo-control trial of pregabalin for the treatment of painful diabetic peripheral neuropathy [abstract P03.049]. Neurology 2000; 54 S3: A177Google Scholar
  150. 150.
    Schneidermann J. Topiramate: pharmacokinetics and pharmacodinamics. Can J Neurol Sci 1998; 25: S3–5Google Scholar
  151. 151.
    Sajwa ZH, Sami N, Warfield CA, et al. Topiramate relieves refractory intercostal neuralgia. Neurology 1999; 52: 1917Google Scholar
  152. 152.
    González-Darder JM, Ortega-Alvaro A, Rui-Franzi I, et al. Antinociceptive effects of phenobarbital in ‘tail-flick’ and deafferentation pain. Anesth Analg 1992; 75: 81–6PubMedGoogle Scholar
  153. 153.
    Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-Methyl-D-aspartate and GABA-A receptors. Ann Neurol 1994; 36: 677–8CrossRefGoogle Scholar
  154. 154.
    Imamura Y, Bennett GJ. Felbamate relieves several abnormal pain sensations in rats with an experimental peripheral neuropathy. J Pharm Exp Ther 1995; 275: 177–82Google Scholar
  155. 155.
    Alves ND, de Castro-Costa CM, de Carvalho AM, et al. Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain. Arq Neuropsiquiatr 1999; 57: 916–20PubMedCrossRefGoogle Scholar
  156. 156.
    Leach JP, Brodie MJ. Tiagabine. Lancet 1998; 351: 203–7PubMedCrossRefGoogle Scholar
  157. 157.
    Giardina WJ, Decker MW, Porsolt RD, et al. An evaluation of the GAB A uptake blocker tiagabine in animal models of neuropathic and nociceptive pain. Drug Dev Res 1998; 44: 106–13CrossRefGoogle Scholar
  158. 158.
    Ipponi A, Lamberti C, Medica A, et al. Tiagabine nociception in rodents depends on GABA-B receptor activation: parallel antinociception testing and medial hypothalamus GABA microdyalisis. Eur J Pharmacol 1999; 368: 205–11PubMedCrossRefGoogle Scholar
  159. 159.
    Yarnitsky D. Quantitative sensory testing. Muscle Nerve 1997; 20: 198–204PubMedCrossRefGoogle Scholar
  160. 160.
    Bouhassira D, Attal N, Willer JC, et al. Painful and painless peripheral sensory neuropathies due to HIV infection: a comparison using quantitative sensory stimulation. Pain 1999; 80: 265–72PubMedCrossRefGoogle Scholar
  161. 161.
    Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the neuropathic pain scale. Neurology 1997; 48: 332–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Ivo W. Tremont-Lukats
    • 1
  • Carla Megeff
    • 2
  • Misha-Miroslav Backonja
    • 1
  1. 1.Neurology DepartmentUniversity of WisconsinMadisonWisconsinUSA
  2. 2.St Louis College of PharmacySt LouisUSA

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