Drugs & Aging

, Volume 11, Issue 5, pp 398–412 | Cite as

How Do Drugs Relieve Neurogenic Pain?

Review Article Drug Therapy


Neurogenic pain is experienced by about 1% of the population. The efficacy of drug treatment for this condition has been poorly evaluated, and only recently have certain treatments been shown to have significant analgesic effects. Monotherapy with topical agents such as capsaicin is not usually sufficient. Oral agents that have proven effective in treating neurogenic pain states include tricyclic antidepressants, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and anticonvulsants. Local anaesthetics, administered intravenously, have been reported to relieve pain in selected patients, but data from controlled trials are sparse.

Multiple mechanisms contribute to the generation of neurogenic pain. In the future, drug treatment for neurogenic pain is likely to target these mechanisms. Recent studies have shown that N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor agonists and nitric oxide synthase inhibitors may become useful in the treatment of neurogenic pain.


Adis International Limited Neuropathic Pain Capsaicin Mexiletine Spinal Cord Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Arnér S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988; 33: 11–23PubMedGoogle Scholar
  2. 2.
    Besson J-M. The pharmacology of pain: twenty-five years of hope, despair, and hope. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th World Congress of Pain. Progress in pain research and management. Seattle: International Association for the Study of Pain (IASP) Press, 1994: 23–39Google Scholar
  3. 3.
    Fields HL, Rowbotham MC. Multiple mechanisms of neuropathic pain: a clinical perspective. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th World Congress on Pain. Progress in pain research and management. Seattle: IASP Press, 1994: 437–54Google Scholar
  4. 4.
    Bowsher D. Neurogenic pain syndromes and their management. Br Med Bull 1991; 47: 644–66PubMedGoogle Scholar
  5. 5.
    Macrae WA, Davies HTO, Crombie IK. Pain: paradigms and treatment. Pain 1992; 49: 289–91PubMedGoogle Scholar
  6. 6.
    Davies HT, Crombie IK, Macrae WA. Polarised views on treating neurogenic pain. Pain 1993; 54: 341–6PubMedGoogle Scholar
  7. 7.
    Davies HT, Crombie IK, Macrae WA. Why use a pain clinic? Management of neurogenic pain before and after referral. J R Soc Med 1994; 87: 382–5PubMedGoogle Scholar
  8. 8.
    Boivie J. Pain in neurology and neurosurgery: introduction. In: Campbell JN, editor. Pain 1996 — an updated review. Seattle: IASP Press, 1996: 19Google Scholar
  9. 9.
    Mersky H. An investigation of pain in psychological illness [thesis]. Oxford: University of Oxford, 1964Google Scholar
  10. 10.
    International Association for the Study of Pain (IASP) X. Pain terms: list with definitions and notes on usage. Pain 1979; 6: 249Google Scholar
  11. 11.
    Wilson PR, Lamer TJ. Pain mechanisms: anatomy and physiology. In: Raj PP, editor. Practical management of pain. St Louis (MO): Mosby-Year Book, 1992: 65–80Google Scholar
  12. 12.
    Samuelsson H, Malmberg F, Eriksson M, et al. Outcomes of epidural morphine treatment in cancer pain: nine years of clinical experience. J Pain Symptom Manage 1995; 10: 105–12PubMedGoogle Scholar
  13. 13.
    Jensen TS. Mechanisms of neuropathic pain. In: Campbell JN, editor. Pain 1996 — an updated review. Seattle: IASP Press, 1996: 77–86Google Scholar
  14. 14.
    Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991; 41: 1024–8PubMedGoogle Scholar
  15. 15.
    Portenoy RK, Foley KM, Inturrisi CE. The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain 1990; 43: 273–86PubMedGoogle Scholar
  16. 16.
    Cherney NI, Thaler HT, Friedlander-Klar H, et al. Opioid responsiveness of cancer pain syndromes caused by neuropathic or nociceptive mechanisms: a combined analysis of controlled, single-dose studies. Neurology 1994; 44: 857–61Google Scholar
  17. 17.
    Foley KM. Misconceptions and controversies regarding the use of opioids in cancer pain. Anticancer Drugs 1995; 6: 4–13PubMedGoogle Scholar
  18. 18.
    Eide P, Stubhaug A, Öje I. The NMDA-antagonist ketamine for the treatment and prevention of acute and chronic postoperative pain. In: Breivik H, editor. Clinical anaesthesiology: postoperadve pain management. London: Saunders, 1995: 539–55Google Scholar
  19. 19.
    Devor M. The pathophysiology and anatomy of damaged nerves. In: Wall PD, Melzack R, editors. Textbook of pain. New York: Churchill Livingstone, 1994: 79–101Google Scholar
  20. 20.
    Woolf CJ, Shordand P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of the myelinated afferents. Nature 1992; 355: 75–7PubMedGoogle Scholar
  21. 21.
    Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992; 48: 261–8PubMedGoogle Scholar
  22. 22.
    Dickenson AH. Central acute pain mechanisms. Ann Med 1995; 27: 223–7PubMedGoogle Scholar
  23. 23.
    Steel JH, Terenghi G, Chung JM, et al. Increased nitric oxide synthetase immunoreactivity in rat dorsal horn ganglia in a neuropathic pain model. Neurosci Lett 1994; 169: 81–4PubMedGoogle Scholar
  24. 24.
    Hökfelt T, Zhang X, Wiesenfeld-Hallin Z. Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci 1994; 17: 22–30PubMedGoogle Scholar
  25. 25.
    Hsieh JC, Belfrage M, Stone-Elander S, et al. Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 1995; 63: 225–36PubMedGoogle Scholar
  26. 26.
    Bennett GJ. Animal models of neuropathic pain. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th World Congress on Pain. Progress in pain research and management. Seattle: IASP Press, 1994: 495–510Google Scholar
  27. 27.
    Ochoa JL, Verdugo RJ, Campero M. Pathophysiological spectrum of organic and psychogenic disorders in neurogenic disorders in neuropathic pain patients fitting the description of causalgia or reflex sympathetic dystrophy. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th World Congress on Pain. Progress in pain research and management. Seattle: IASP Press, 1994: 483–94Google Scholar
  28. 28.
    Sang CN, Gracely RH, Max MB, et al. Capsaicin-evoked mechanical allodynia and hyperalgesia cross nerve territories. Anesthesiology 1996; 85: 491–6PubMedGoogle Scholar
  29. 29.
    Hansson P. Neurogenic pain: diagnosis and treatment. Pain Clin Updates 1994; II: 1–4Google Scholar
  30. 30.
    Boivie J. Central pain syndromes. In: Campbell JN, editor. Pain 1996 — an updated review. Seattle: IASP Press, 1996: 23–9Google Scholar
  31. 31.
    Boivie J, Leijon G, Johansson L. Central post-stroke pain — a study of the mechanisms through analysis of the sensory abnormalities. Pain 1989; 37: 173–85PubMedGoogle Scholar
  32. 32.
    Vestergaard K, Nielsen J, Andersen G, et al. Sensory abnormalities in consecutive, unselected patients with central post-stroke pain. Pain 1995; 61: 177–86PubMedGoogle Scholar
  33. 33.
    Andersen G, Vestergaard K, Ingeman Nielsen M, et al. Incidence of central post-stroke pain. Pain 1995; 61: 187–93PubMedGoogle Scholar
  34. 34.
    Rowbotham MC. Topical analgesic agents. In: Fields HL, Liebeskind JC, editors. Progress in pain research and management. Seattle: IASP Press, 1994: 211–29Google Scholar
  35. 35.
    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(4): 317–28PubMedGoogle Scholar
  36. 36.
    Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations. Pharmacol Rev 1986 Sep; 38: 179–226PubMedGoogle Scholar
  37. 37.
    McMahon SB, Lewin G, Bloom SR. The consequences of long-term topical capsaicin application in the rat. Pain 1991; 44: 301–10PubMedGoogle Scholar
  38. 38.
    Watson CPN. The treatment of postherpetic neuralgia. Neurology 1995; 45 Suppl. 8: S58–60PubMedGoogle Scholar
  39. 39.
    Low PA, Opfer-Gehring TL, Dyck PJ, et al. Double-blind, placebo-controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy. Pain 1995; 62: 163–8PubMedGoogle Scholar
  40. 40.
    Watson CP. Topical capsaicin as an adjuvant analgesic. J Pain Symptom Manage 1994; 9: 425–33PubMedGoogle Scholar
  41. 41.
    Bonica J. Causalgia and other reflex dystrophies. In: Bonica J, Liebeskind J, Albe-Fessard D, editors. Advances in pain research and therapy. New York: Raven Press, 1979: 141–66Google Scholar
  42. 42.
    Hannington-Kiff JG. Intravenous regional sympathetic block with guanethidine. Lancet 1974; I: 1019–20Google Scholar
  43. 43.
    Torebjörk E, Wahren L-K, Wallin G, et al. Noradrenaline-evoked pain in neuralgia. Pain 1995; 63: 11–20PubMedGoogle Scholar
  44. 44.
    Wahren LK, Gordh T, Torebjörk E. Effects of regional intravenous guanethidine in patients with neuralgia in the hand: a follow-up over a decade. Pain 1995; 62: 379–85PubMedGoogle Scholar
  45. 45.
    Chang CC, Costa E, Brodie BB. Interaction of guanethidine with adrenergic neurons. J Pharmacol Exp Ther 1965; 147: 303–12PubMedGoogle Scholar
  46. 46.
    Casale R, Glynn C, Buonocore M. The role of ischemia in the analgesia which follows Bier’s block technique. Pain 1992; 50: 169–75PubMedGoogle Scholar
  47. 47.
    Valentin N. Reflex sympathetic dystrophy treated with guanethidine: time for a change of name and strategy. Acta Anaesthesiol Scand 1996; 40: 1171–2PubMedGoogle Scholar
  48. 48.
    Paoli F, Darcourt G, Corsa P. Note préliminaire sur l’action de I’imipramine dans les états doloreux. Rev Neurol 1960; 2: 503–4Google Scholar
  49. 49.
    Biegon A, Samuel D. Interaction of tricyclic antidepressants with opiate receptors. Biochem Pharmacol 1980; 29: 460–2PubMedGoogle Scholar
  50. 50.
    Isenberg KE, Cicero TJ. Possible involvement of opiate receptors in the pharmacological profiles of antidepressant compounds. Eur J Pharmacol 1984; 103: 57–63PubMedGoogle Scholar
  51. 51.
    Eisenach JC, Gebhart GF. Intrathecal amitriptyline: antinociceptive interactions with IV morphine and intrathecal Clonidine, neostigmine and carbamylcholine in rats. Anesthesiology 1995; 83: 1036–45PubMedGoogle Scholar
  52. 52.
    Bromm B, Meier W, Scharein E. Imipramine reduces experimental pain. Pain 1986; 25: 245–57PubMedGoogle Scholar
  53. 53.
    Poulsen L, Arendt Nielsen L, Brosen K, et al. The hypoalgesic effect of imipramine in different human experimental pain models. Pain 1995; 60: 287–93PubMedGoogle Scholar
  54. 54.
    Coquoz D, Porchet HC, Dayer P. Central analgesic effects of antidepressant drugs with various mechanisms of action: desipramine, fluvoxamine and moclobemide. Schweiz Med Wochenschr 1991; 121: 1843–5PubMedGoogle Scholar
  55. 55.
    Eisenach JC. Three novel spinal analgesics: Clonidine, neosdgmine, amitriptyline. Reg Anesth 1996; 21: 81–3PubMedGoogle Scholar
  56. 56.
    Max MB. Treatment of post-herpetic neuralgia: antidepressants. Ann Neurol 1994; 35 Suppl.: S50–3PubMedGoogle Scholar
  57. 57.
    Bryson HM, Wilde MI. Amitriptyline: a review of its pharmacological properdes and therapeutic use in chronic pain states. Drugs Aging 1996; 8(6): 459–76PubMedGoogle Scholar
  58. 58.
    McQuay HJ, Tramèr M, Nye BA, et al. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68: 217–27PubMedGoogle Scholar
  59. 59.
    Yaksh TL, Aimone LD. The central pharmacology of pain transmission. In: Wall PD, Melzack R, editors. The textbook of pain. Lontion: Churchill Livingstone, 1989: 118–205Google Scholar
  60. 60.
    Max MB. Antidepressants as analgesics. In: Fields HL, Liebeskind JC, editors. Progress in pain research and management. Seattle: IASP Press, 1994: 229–46Google Scholar
  61. 61.
    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: 135–44PubMedGoogle Scholar
  62. 62.
    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: 547–52PubMedGoogle Scholar
  63. 63.
    Kalso E, Tasmuth T, Neuvonen PJ. Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. Pain 1995; 64: 293–302Google Scholar
  64. 64.
    McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 1993; 48: 281–5PubMedGoogle Scholar
  65. 65.
    Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Hardman JG, Limbird LE, Molinoff PB, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 431–59Google Scholar
  66. 66.
    Ray WA, Griffin MR, Schaffner W, et al. Psychotropic drug use and the risk of hip fracture. N Engl J Med 1987; 316: 363–9PubMedGoogle Scholar
  67. 67.
    Barbour CM, Tovell RM. Experiences with procaine administered intravenously. Ann Intern Med 1948; 10: 514–23Google Scholar
  68. 68.
    Boas RA, Covino BG, Shahnarian A. Analgesic responses to i.v. lidocaine. Br J Anaesth 1982; 54: 501–5PubMedGoogle Scholar
  69. 69.
    Edwards WT, Habib F, Burney RG, et al. Intravenous lidocaine in the management of various chronic pain states. Reg Anesth 1985; 10: 1–6Google Scholar
  70. 70.
    Kastrup J, Petersen P, Dejgard AEA. Intravenous lidocaine infusion — a new treatment of chronic painful neuropathy. Pain 1987; 28: 69–75PubMedGoogle Scholar
  71. 71.
    Ferrante FM, Paggioli J, Cherukuri S, et al. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg 1996; 82: 91–7PubMedGoogle Scholar
  72. 72.
    Chabal C, Russell LC, Burchiel KJ. The effect of intravenous lidocaine, tocainide and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 1989; 38: 333–8PubMedGoogle Scholar
  73. 73.
    Devor M, Wall P, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992; 48: 261–8PubMedGoogle Scholar
  74. 74.
    Woolf CJ, Wiesenfeld-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: 361–74PubMedGoogle Scholar
  75. 75.
    Arnér S, Lindblom U, Meyerson BA, et al. Prolonged relief of neuralgia after regional anesthetic blocks: a call for further experimental and systematic clinical studies. Pain 1990; 43: 287–97PubMedGoogle Scholar
  76. 76.
    Brose WG, Cousins MJ. Subcutaneous lidocaine for treatment of neuropathic cancer pain. Pain 1991; 45: 145–8PubMedGoogle Scholar
  77. 77.
    Devulder JE, Ghys L, Dhondt W, et al. Neuropathic pain in a cancer patient responding to subcutaneously administered lignocaine. Clin J Pain 1993; 9: 220–3PubMedGoogle Scholar
  78. 78.
    Marchettini P, Lacerenza M, Marangoni C, et al. Lidocaine test in neuralgia. Pain 1992; 48: 377–82PubMedGoogle Scholar
  79. 79.
    Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988; I: 9–11Google Scholar
  80. 80.
    Stacke H, Meyer UE, Schumacher HE, et al. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care 1992; 15: 1550–5Google Scholar
  81. 81.
    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: 513–7PubMedGoogle Scholar
  82. 82.
    Impact Research Group. International Mexiletine and Placebo Antiarrhythmic Coronary Trial: I. Report on arrhythmia and other findings. J Am Coll Cardiol 1984; 4: 1148–63Google Scholar
  83. 83.
    Lindström P, Lindblom U. The analgesic effect of tocainide in trigeminal neuralgia. Pain 1987; 28: 45–50PubMedGoogle Scholar
  84. 84.
    McQuay H, Carroll D, Jadad AR, et al. Anticonvulsant drugs for management of pain: a systematic review. BMJ 1995; 311: 1047–52PubMedGoogle Scholar
  85. 85.
    Blom S. Trigeminal neuralgia: its treatment with a new anticonvulsant drug (G-32883). Lancet 1962 Apr; I: 839–40Google Scholar
  86. 86.
    McNamara JO. Drugs effective in the therapy of the epilepsies. In: Hardman JG, Limbird LE, Molinoff PB, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 461–86Google Scholar
  87. 87.
    Berde CH. New and old anticonvulsants for the management of pain. IASP Newsletter 1997 Jan/Feb: 3–5Google Scholar
  88. 88.
    Blom S. Tic douloureux treated with new anticonvulsant. Arch Neurol 1963; 9: 285–90PubMedGoogle Scholar
  89. 89.
    Patsalos PN. Phenobarbitone to gabapentin: a guide to 82 years of anti-epileptic drug pharmacokinetic interactions. Seizure 1994; 3: 163–70PubMedGoogle Scholar
  90. 90.
    Boivie J. Antiepileptic drugs for the treatment of neuropathic pain. In: Campbell JN, editor. Pain 1996 — an updated review. Seattle: IASP Press, 1996: 21–2Google Scholar
  91. 91.
    Benson RF, Parris WCV. Efficacy of gabapentin for neuropathic pain [abstract]. 8th World Congress on Pain. Seattle: IASP Press, 1996: 73Google Scholar
  92. 92.
    Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain 1996; 12: 56–8PubMedGoogle Scholar
  93. 93.
    Eisenberg E, Alon N. Lamotrigine in the treatment of painful diabetic neuropathy [abstract]. 8th World Congress on Pain. Seattle: IASP Press, 1996: 372Google Scholar
  94. 94.
    Wadelius M, Karlsson T, Wadelius C, et al. Lamotrigine and toxic epidermal necrolysis. Lancet 1996; 348: 1041PubMedGoogle Scholar
  95. 95.
    Kristensen J, Gordh T. Modulation of NMDA receptor function for pain treatment. In: Biebuyck JF, Lynch III C, Maze M, et al., editors. Anesthesia: biological foundations. Philadelphia: Lippencott-Raven. In pressGoogle Scholar
  96. 96.
    Dickenson AH. A cure for wind-up: NMDA receptor antagonists as potential analgesics. Trends Pharmacol Sci 1990; 11: 307–9PubMedGoogle Scholar
  97. 97.
    Woolf CJ, Thompson SWN. 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: 293–9PubMedGoogle Scholar
  98. 98.
    Yaksh TL. Epidural ketamine: a useful, mechanistically novel adjuvant for epidural morphine? Reg Anesth 1996; 21: 508–13PubMedGoogle Scholar
  99. 99.
    Eide PK, Stubhaug A, Oye I, et al. Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia. Pain 1995; 61: 221–8PubMedGoogle Scholar
  100. 100.
    Mathisen LC, Skjelbred P, Skoglund LA, et al. Effects of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain 1995; 61: 215–20PubMedGoogle Scholar
  101. 101.
    Stannard CF, Porter GE. Ketamine hydrochloride in the treatment of phantom limb pain. Pain 1993; 54: 227–30PubMedGoogle Scholar
  102. 102.
    Stubhaug A, Breivik H. Longterm treatment of chronic neuropathic pain with the NMDA (N-methyl-D-aspartate) receptor antagonist ketamine. Acta Anaesthesiol Scand 1997; 41: 329–31PubMedGoogle Scholar
  103. 103.
    McQuay HJ, Carroll D, Jadad AR, et al. Dextromethorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design. Pain 1994; 59: 127–33PubMedGoogle Scholar
  104. 104.
    Nelson KA, Park KM, Robinovitz E, et al. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 1997; 48: 1212–8PubMedGoogle Scholar
  105. 105.
    Meller ST. Ketamine, relief from chronic pain through actions at the NMDA receptor? Pain 1996; 68: 435–6PubMedGoogle Scholar
  106. 106.
    Kristensen JD, Svensson BA, Gordh Jr T. The NMDA antagonist CPP abolishes neurogenic ‘wind-up pain’ after intrathecal administration in humans. Pain 1992; 51: 249–53PubMedGoogle Scholar
  107. 107.
    Eisenach JC, De Kock M, Klimscha W. Alfa2-adrenergic agonists for regional anesthesia. Anesthesiology 1996; 85: 655–74PubMedGoogle Scholar
  108. 108.
    Xu Z, Li P, Tong C, et al. Location and characteristics of nitric oxide synthase in sheep spinal cord and its interaction with alpha2-adrenergic and cholinergic antinociception. Anesthesiology 1996; 84: 890–9PubMedGoogle Scholar
  109. 109.
    Tamsen A, Gordh T. Epidural Clonidine produces analgesia. Lancet 1984; II: 231–2Google Scholar
  110. 110.
    Eisenach JC, DuPen S, Dubois M, et al. Epidural Clonidine analgesia for intractable cancer pain: the Epidural Clonidine Study Group. Pain 1995; 61: 391–9PubMedGoogle Scholar
  111. 111.
    Rauck RL, Eisenach JC, Jackson K, et al. Epidural Clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology 1993; 79: 1163–9PubMedGoogle Scholar
  112. 112.
    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: 267–74PubMedGoogle Scholar
  113. 113.
    Hanks GW, Justins DM. Cancer pain management. Lancet 1992; 339: 1031–5PubMedGoogle Scholar
  114. 114.
    Samuelsson H, Hedner T. Pain characterization in cancer patients and the analgesic response to epidural morphine. Pain 1991; 46: 3–8PubMedGoogle Scholar
  115. 115.
    Hanks GW, Forbes K. Opioid responsiveness. Acta Anaesthesiol Scand 1997; 41: 154–8PubMedGoogle Scholar
  116. 116.
    Hegarty A, Portenoy RK. Pharmacotherapy of neuropathic pain. Semin Neurol 1994; 14: 213–24PubMedGoogle Scholar
  117. 117.
    Rowbotham MC, Reisner Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991; 41: 1024–8PubMedGoogle Scholar
  118. 118.
    Choca JI, Proudfit HK, Green RD. Idendfication of A1 and A2 adenosine receptors in the rat spinal cord. J Pharmacol Exp Ther 1987; 242: 905–10PubMedGoogle Scholar
  119. 119.
    Fastbom J, Pazos A, Probst A, et al. Adenosine A1 receptors in the human brain: a quantitative autoradiographic study. Neuroscience 1987; 22: 827–39PubMedGoogle Scholar
  120. 120.
    Van Calker D, Müller M, Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 1979; 33: 999–1005PubMedGoogle Scholar
  121. 121.
    Karlsten R, Post C, Hide I, et al. The andnociceptive effect of intrathecally administered adenosine analogs in mice correlates with the affinity for the A1-adenosine receptor. Neurosci Lett 1991; 121: 267–70PubMedGoogle Scholar
  122. 122.
    Yamamoto T, Yaksh TL. Spinal pharmacology of thermal hyperesthesia induced by incomplete ligation of sciatic nerve: I. Opioid and nonopioid receptors. Anesthesiology 1991; 75: 817–26PubMedGoogle Scholar
  123. 123.
    Sosnowski M, Yaksh TL. Role of spinal adenosine receptors in modulating the hyperesthesia produced by spinal glycine receptor antagonism. Anesth Analg 1989; 69: 587–92PubMedGoogle Scholar
  124. 124.
    Lee Y-W, Yaksh TL. Pharmacology of the spinal adenosine receptor which mediates the antiallodynic action of intrathecal adenosine agonists. J Pharmacol Exp Ther 1996; 277: 1642–8PubMedGoogle Scholar
  125. 125.
    Reeve AJ, Dickenson AH. The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurons in the anaesthetized rat. Br J Pharmacol 1995; 116: 2221–8PubMedGoogle Scholar
  126. 126.
    Belfrage M, Sollevi A, Segerdahl M, et al. Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in patients with peripheral neuropathic pain. Anesth Analg 1995; 81: 713–7PubMedGoogle Scholar
  127. 127.
    Sollevi A, Belfrage M, Lundeberg T, et al. Systemic adenosine infusion: a new treatment modality to alleviate neuropathic pain. Pain 1995; 61: 155–8PubMedGoogle Scholar
  128. 128.
    Karlsten R, Gordh T. An A1-selective adenosine agonist abolishes allodynia elicited by vibration and touch after intrathecal injection. Anesth Analg 1995; 80: 844–7PubMedGoogle Scholar
  129. 129.
    Guieu R, Peragut JC, Roussel P, et al. Adenosine and neuropathic pain. Pain 1996; 68: 271–4PubMedGoogle Scholar
  130. 130.
    Meller ST, Gebhart GF. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993; 52: 127–36PubMedGoogle Scholar
  131. 131.
    Siegan JB, Hama AT, Sagen J. Alteration in the rat spinal cord c-GMP by peripheral nerve injury and adrenal medullary transplantation. Neurosci Lett 1996; 215: 49–52PubMedGoogle Scholar
  132. 132.
    Meyerson BA. Mechanisms of spinal cord stimulation as pain treatment. In: Campbell JN, editor. Pain 1996 — an updated review. Seattle: IASP Press, 1996: 207–15Google Scholar
  133. 133.
    Nitescu P, Sjöberg M, Appelgren L, et al. Complications of intrathecal opioids and bupivacaine in the treatment of ‘refractory’ cancer pain. Clin J Pain 1995; 11: 45–62PubMedGoogle Scholar

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© Adis International Limited 1997

Authors and Affiliations

  1. 1.Multidisciplinary Pain Treatment Centre, Department of AnaesthesiologyUniversity HospitalUppsalaSweden

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