European Neuropsychopharmacology
Volume 22, Issue 2 , Pages 81-91 , February 2012

Mechanisms of neuropathic pain

Received 8 November 2010 ,Revised 12 April 2011 ,Accepted 14 May 2011.

References 

  1. Abram SE, Yaksh TL. Systemic lidocaine blocks nerve injury-induced hyperalgesia and nociceptor-driven spinal sensitization in the rat. Anesthesiology. 1994;80:383–391discussion 325A
  2. Amir R, Michaelis M, Devor M. Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and neuropathic pain. J Neurosci. 1999;19:8589–8596
  3. Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G. Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet. 2002;359:1655–1660
  4. Bird EV, Robinson PP, Boissonade FM. Na(v)1.7 sodium channel expression in human lingual nerve neuromas. Arch Oral Biol. 2007;52:494–502
  5. Birklein F, Weber M, Ernst M, Riedl B, Neundorfer B, Handwerker HO. Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS). Pain. 2000;87:227–234
  6. Bouhassira D. Definition and classification of neuropathic pain. Presse Med. 2008;37:311–314
  7. Brochu RM, Dick IE, Tarpley JW, McGowan E, Gunner D, Herrington J, et al. Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats. Mol Pharmacol. 2006;69:823–832
  8. Bruggemann J, Galhardo V, Apkarian AV. Immediate reorganization of the rat somatosensory thalamus after partial ligation of sciatic nerve. J Pain. 2001;2:220–228
  9. Cepeda, M.S., Carr, D.B., Lau, J., 2005. Local anesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev, CD004598.
  10. Costigan M, Woolf CJ. No DREAM, No pain. Closing the spinal gate. Cell. 2002;108:297–300
  11. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006;444:894–898
  12. Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci. 2002;3:655–666
  13. Craig AD, Bushnell MC. The thermal grill illusion: unmasking the burn of cold pain. Science. 1994;265:252–255
  14. Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007;14:952–970
  15. Cui JG, O'Connor WT, Ungerstedt U, Linderoth B, Meyerson BA. Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. Pain. 1997;73:87–95
  16. Cummins TR, Sheets PL, Waxman SG. The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain. 2007;131:243–257
  17. D'Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth. 2008;101:8–16
  18. Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT. Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain. 2007;8:315–324
  19. Dubinsky RM, Miyasaki J. Assessment: efficacy of transcutaneous electric nerve stimulation in the treatment of pain in neurologic disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74:173–176
  20. Eide PK, Jorum E, Stubhaug A, Bremnes J, Breivik H. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain. 1994;58:347–354
  21. Eisenberg E, Lurie Y, Braker C, Daoud D, Ishay A. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology. 2001;57:505–509
  22. Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron. 2006;52:767–774
  23. Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002;1:182–189
  24. Flor H, Braun C, Elbert T, Birbaumer N. Extensive reorganization of primary somatosensory cortex in chronic back pain patients. Neurosci Lett. 1997;224:5–8
  25. Flor H, Denke C, Schaefer M, Grusser S. Effect of sensory discrimination training on cortical reorganisation and phantom limb pain. Lancet. 2001;357:1763–1764
  26. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 1995;375:482–484
  27. Flor H, Nikolajsen L, Staehelin Jensen T. Phantom limb pain: a case of maladaptive CNS plasticity?. Nat Rev Neurosci. 2006;7:873–881
  28. Frettloh J, Huppe M, Maier C. Severity and specificity of neglect-like symptoms in patients with complex regional pain syndrome (CRPS) compared to chronic limb pain of other origins. Pain. 2006;124:184–189
  29. Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep. 2009;13:185–190
  30. Freynhagen R, Rolke R, Baron R, Tolle TR, Rutjes AK, Schu S, et al. Pseudoradicular and radicular low-back pain–a disease continuum rather than different entities? Answers from quantitative sensory testing. Pain. 2008;135:65–74
  31. Fundytus ME, Fisher K, Dray A, Henry JL, Coderre TJ. In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats. Neuroreport. 1998;9:731–735
  32. Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anaesthesiol. 2007;20:456–472
  33. Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. Cmaj. 2006;175:265–275
  34. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116:109–118
  35. Guan Y, Wacnik PW, Yang F, Carteret AF, Chung CY, Meyer RA, et al. Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats. Anesthesiology. 2010;113:1392–1405
  36. Guerrini R, Parmeggiani L. Topiramate and its clinical applications in epilepsy. Expert Opin Pharmacother. 2006;7:811–823
  37. Guo LH, Schluesener HJ. The innate immunity of the central nervous system in chronic pain: the role of Toll-like receptors. Cell Mol Life Sci. 2007;64:1128–1136
  38. Han C, Rush AM, Dib-Hajj SD, Li S, Xu Z, Wang Y, et al. Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann Neurol. 2006;59:553–558
  39. Hansson P, Backonja M, Bouhassira D. Usefulness and limitations of quantitative sensory testing: clinical and research application in neuropathic pain states. Pain. 2007;129:256–259
  40. Hong S, Morrow TJ, Paulson PE, Isom LL, Wiley JW. Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat. J Biol Chem. 2004;279:29341–29350
  41. Hong S, Wiley JW. Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1. J Biol Chem. 2005;280:618–627
  42. Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain. 1995;63:225–236
  43. Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron. 2007;55:365–376
  44. Hudson LJ, Bevan S, Wotherspoon G, Gentry C, Fox A, Winter J. VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. Eur J Neurosci. 2001;13:2105–2114
  45. Iadarola MJ, Max MB, Berman KF, Byas-Smith MG, Coghill RC, Gracely RH, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain. 1995;63:55–64
  46. Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med. 2004;10:712–718
  47. Jarvis B, Coukell AJ. Mexiletine. A review of its therapeutic use in painful diabetic neuropathy. Drugs. 1998;56:691–707
  48. Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, et al. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci USA. 2007;104:8520–8525
  49. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413:203–210
  50. Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med. 2008;14:331–336
  51. Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci. 2002;22:9086–9098
  52. Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008;9:1173–1201
  53. Knabl J, Witschi R, Hosl K, Reinold H, Zeilhofer UB, Ahmadi S, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature. 2008;451:330–334
  54. Knecht S, Henningsen H, Hohling C, Elbert T, Flor H, Pantev C, et al. Plasticity of plasticity? Changes in the pattern of perceptual correlates of reorganization after amputation. Brain. 1998;121(Pt 4):717–724
  55. Koppert W, Dern SK, Sittl R, Albrecht S, Schuttler J, Schmelz M. A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine. Anesthesiology. 2001;95:395–402
  56. Kurvers HA, Jacobs MJ, Beuk RJ, Van den Wildenberg FA, Kitslaar PJ, Slaaf DW, et al. Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time. Pain. 1995;60:333–340
  57. Lai J, Luo MC, Chen Q, Ma S, Gardell LR, Ossipov MH, et al. Dynorphin A activates bradykinin receptors to maintain neuropathic pain. Nat Neurosci. 2006;9:1534–1540
  58. Lingueglia E. Acid-sensing ion channels in sensory perception. J Biol Chem. 2007;282:17325–17329
  59. Lumpkin EA, Caterina MJ. Mechanisms of sensory transduction in the skin. Nature. 2007;445:858–865
  60. Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, et al. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci. 2001;21:1868–1875
  61. Maihofner C, Baron R, DeCol R, Binder A, Birklein F, Deuschl G, et al. The motor system shows adaptive changes in complex regional pain syndrome. Brain. 2007;130:2671–2687
  62. Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Patterns of cortical reorganization in complex regional pain syndrome. Neurology. 2003;61:1707–1715
  63. Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurology. 2004;63:693–701
  64. Maihofner C, Neundorfer B, Birklein F, Handwerker HO. Mislocalization of tactile stimulation in patients with complex regional pain syndrome. J Neurol. 2006;253:772–779
  65. Malan TP, Ossipov MH, Gardell LR, Ibrahim M, Bian D, Lai J, et al. Extraterritorial neuropathic pain correlates with multisegmental elevation of spinal dynorphin in nerve-injured rats. Pain. 2000;86:185–194
  66. Manfredi M, Bini G, Cruccu G, Accornero N, Berardelli A, Medolago L. Congenital absence of pain. Arch Neurol. 1981;38:507–511
  67. Matthews EA, Dickenson AH. Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy. Pain. 2001;92:235–246
  68. McCabe CS, Haigh RC, Blake DR. Mirror visual feedback for the treatment of complex regional pain syndrome (type 1). Curr Pain Headache Rep. 2008;12:103–107
  69. McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain. 2006;10:127–135
  70. Miao FJ, Janig W, Levine J. Role of sympathetic postganglionic neurons in synovial plasma extravasation induced by bradykinin. J Neurophysiol. 1996;75:715–724
  71. Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51:240–264
  72. Ossipov MH, Lai J, Malan TP, Porreca F. Spinal and supraspinal mechanisms of neuropathic pain. Ann N Y Acad Sci. 2000;909:12–24
  73. Pan HL, Wu ZZ, Zhou HY, Chen SR, Zhang HM, Li DP. Modulation of pain transmission by G-protein-coupled receptors. Pharmacol Ther. 2008;117:141–161
  74. Pezet S, McMahon SB. Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci. 2006;29:507–538
  75. Ramachandran VS, Altschuler EL. The use of visual feedback, in particular mirror visual feedback, in restoring brain function. Brain. 2009;132:1693–1710
  76. Ramachandran VS, Stewart M, Rogers-Ramachandran DC. Perceptual correlates of massive cortical reorganization. Neuroreport. 1992;3:583–586
  77. Ramer MS, Thompson SW, McMahon SB. Causes and consequences of sympathetic basket formation in dorsal root ganglia. Pain. 1999;Suppl 6:S111–S120
  78. Raskin P, Donofrio PD, Rosenthal NR, Hewitt DJ, Jordan DM, Xiang J, et al. Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects. Neurology. 2004;63:865–873
  79. Rauck RL, Wallace MS, Leong MS, Minehart M, Webster LR, Charapata SG, et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. 2006;31:393–406
  80. Rice AS, Hill RG. New treatments for neuropathic pain. Annu Rev Med. 2006;57:535–551
  81. Ro LS, Chen ST, Tang LM, Jacobs JM. Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve. Pain. 1999;79:265–274
  82. Rogers M, Tang L, Madge DJ, Stevens EB. The role of sodium channels in neuropathic pain. Semin Cell Dev Biol. 2006;17:571–581
  83. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10:77–88
  84. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110:697–706
  85. Roza C, Laird JM, Souslova V, Wood JN, Cervero F. The tetrodotoxin-resistant Na+channel Nav1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J Physiol. 2003;550:921–926
  86. Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science. 1991;251:1608–1610
  87. Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjork E, Handwerker H. Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci. 1995;15:333–341
  88. Scholz J, Mannion RJ, Hord DE, Griffin RS, Rawal B, Zheng H, et al. A novel tool for the assessment of pain: validation in low back pain. PLoS Med. 2009;6:e1000047
  89. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10:1361–1368
  90. Seifert F, Kiefer G, DeCol R, Schmelz M, Maihofner C. Differential endogenous pain modulation in complex-regional pain syndrome. Brain. 2009;132:788–800
  91. Seifert F, Maihofner C. Central mechanisms of experimental and chronic neuropathic pain: findings from functional imaging studies. Cell Mol Life Sci. 2009;66:375–390
  92. Shinder V, Govrin-Lippmann R, Cohen S, Belenky M, Ilin P, Fried K, et al. Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1999;28:743–761
  93. Simpson DM, McArthur JC, Olney R, Clifford D, So Y, Ross D, et al. Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial. Neurology. 2003;60:1508–1514
  94. Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184–187
  95. Susser E, Sprecher E, Yarnitsky D. Paradoxical heat sensation in healthy subjects: peripherally conducted by A delta or C fibres?. Brain. 1999;122(Pt 2):239–246
  96. Suzuki R, Hunt SP, Dickenson AH. The coding of noxious mechanical and thermal stimuli of deep dorsal horn neurones is attenuated in NK1 knockout mice. Neuropharmacology. 2003;45:1093–1100
  97. Tal M, Wall PD, Devor M. Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat. Brain Res. 1999;824:218–223
  98. Tecchio F, Padua L, Aprile I, Rossini PM. Carpal tunnel syndrome modifies sensory hand cortical somatotopy: a MEG study. Hum Brain Mapp. 2002;17:28–36
  99. Thienel U, Neto W, Schwabe SK, Vijapurkar U. Topiramate in painful diabetic polyneuropathy: findings from three double-blind placebo-controlled trials. Acta Neurol Scand. 2004;110:221–231
  100. Torebjork E, Wahren L, Wallin G, Hallin R, Koltzenburg M. Noradrenaline-evoked pain in neuralgia. Pain. 1995;63:11–20
  101. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7:281–289
  102. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377–391
  103. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–1635
  104. Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis. Anesth Analg. 2005;101:1738–1749
  105. Tsuda M, Inoue K, Salter MW. Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. Trends Neurosci. 2005;28:101–107
  106. Ueda H. Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination. Mol Pain. 2008;4:11
  107. Vanderah TW, Gardell LR, Burgess SE, Ibrahim M, Dogrul A, Zhong CM, et al. Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. J Neurosci. 2000;20:7074–7079
  108. Vanegas H, Schaible HG. Descending control of persistent pain: inhibitory or facilitatory?. Brain Res Brain Res Rev. 2004;46:295–309
  109. Vestergaard K, Andersen G, Gottrup H, Kristensen BT, Jensen TS. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology. 2001;56:184–190
  110. White DM, Leah JD, Zimmermann M. The localization and release of substance P and calcitonin gene-related peptide at nerve fibre endings in rat cutaneous nerve neuroma. Brain Res. 1989;503:198–204
  111. Wiffen, P.J., Rees, J., 2007. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev, CD006044.
  112. Wood JN, Boorman JP, Okuse K, Baker MD. Voltage-gated sodium channels and pain pathways. J Neurobiol. 2004;61:55–71
  113. Woolf CJ, Decosterd I. Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients. Pain. 1999;Suppl 6:S141–S147
  114. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999;353:1959–1964
  115. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288:1765–1769
  116. Wu WL, Burnett DA, Domalski M, Greenlee WJ, Li C, Bertorelli R, et al. Discovery of orally efficacious tetracyclic metabotropic glutamate receptor 1 (mGluR1) antagonists for the treatment of chronic pain. J Med Chem. 2007;50:5550–5553
  117. Xing H, Chen M, Ling J, Tan W, Gu JG. TRPM8 mechanism of cold allodynia after chronic nerve injury. J Neurosci. 2007;27:13680–13690
  118. Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet. 2004;41:171–174
  119. Yarnitsky D. Quantitative sensory testing. Muscle Nerve. 1997;20:198–204
  120. Zeilhofer HU. Loss of glycinergic and GABAergic inhibition in chronic pain–contributions of inflammation and microglia. Int Immunopharmacol. 2008;8:182–187
  121. Zeilhofer, H.U., Witschi, R., Hosl, K., 2009. Subtype-selective GABA(A) receptor mimetics-novel antihyperalgesic agents? J Mol Med.
  122. Zimmermann K, Leffler A, Babes A, Cendan CM, Carr RW, Kobayashi J, et al. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature. 2007;447:855–858
  123. Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429:23–37
  124. Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA. Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci. 2007;10:277–279

PII: S0924-977X(11)00104-0

doi: 10.1016/j.euroneuro.2011.05.005

European Neuropsychopharmacology
Volume 22, Issue 2 , Pages 81-91 , February 2012