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Rôle des canaux sodium des neurones afférents primaires dans les douleurs neuropathiques périphériques

The role of voltage-gated sodium channels in neuropathic pain

  • Published:
Douleur et Analgésie

Résumé

Les douleurs neuropathiques, consécutives à une lésion du système nerveux, répondent mal aux traitements antalgiques usuels et souffrent d’une prise en charge thérapeutique insuffisante. Une des conséquences d’une lésion nerveuse périphérique est l’apparition d’activités électriques anormales au sein des fibres afférentes primaires lésées. Les données expérimentales réunies au cours de ces dernières années ont permis de révéler la multiplicité et la complexité des remaniements périphériques et centraux potentiellement impliqués dans le déterminisme de ces douleurs. Il existe notamment des modifications de la répartition spatiale, de l’expression et de l’activité de certaines isoformes des canaux sodiques au niveau des fibres lésées. Le développement de médicaments spécifiquement destinés à agir sur ces canaux permettra sans doute d’obtenir des composés dotés d’une efficacité thérapeutique accrue et dépourvus de certains effets indésirables.

Abstract

Management of neuropathic pain remains a major clinical challenge. Clinical and experimental data indicate that changes in the expression of voltage-gated sodium channels play a key role in the pathogenesis of neuropathic pain. Several of the sodium channel isoforms that are implicated in neuropathic pain states are selectively expressed in somatosensory primary afferent neurons. This restricted expression pattern raises the possibility that isoform-specific drugs might be analgesic and lack the cardiotoxicity and neurotoxicity that limit the use of current sodium channel blockers.

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Références

  1. Abram SE, Yaksh TL (1994) Systemic lidocaine blocks nerve injuryinduced hyperalgesia and nociceptor-driven spinal sensitization in the rat. Anesthesiology 80(2): 383–391

    Article  PubMed  CAS  Google Scholar 

  2. Amaya F, Wang H, Costigan M, et al. (2006) The voltage-gated sodium channel Nav1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 26(50): 12852–12860

    Article  PubMed  CAS  Google Scholar 

  3. Arnér S, Lindblom U, Meyerson BA, Molander C (1990) Prolonged relief of neuralgia after regional anesthetic blocks. A call for further experimental and systematic clinical studies. Pain 43(3): 287–297

    Article  PubMed  Google Scholar 

  4. Beckh S (1990) Differential expression of sodium channel mRNAs in rat peripheral nervous system and innervated tissues. FEBS Lett 262(2): 317–322

    Article  PubMed  CAS  Google Scholar 

  5. Black JA, Cummins TR, Plumpton C, et al. (1999) Up regulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons. J Neurophysiol 82(5): 2776–2785

    PubMed  CAS  Google Scholar 

  6. Black JA, Dib-Hajj S, McNabola K, et al. (1996) Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. Brain Res Mol Brain Res 43(1–2): 117–131

    Article  PubMed  CAS  Google Scholar 

  7. Black JA, Liu S, Tanaka M, et al. (2004) Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108(3): 237–247

    Article  PubMed  CAS  Google Scholar 

  8. Black JA, Renganathan M, Waxman SG (2002) Sodium channel Nav1.6 is expressed along non-myelinated axons and it contributes to conduction. Brain Res Mol Brain Res 105(1–2): 19–28

    Article  PubMed  CAS  Google Scholar 

  9. Blackburn-Munro G, Fleetwood-Walker SM (1999) The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats. Neuroscience 90(1): 153–164

    Article  PubMed  CAS  Google Scholar 

  10. Blair NT, Bean BP (2003) Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci 23(32): 10338–10350

    PubMed  CAS  Google Scholar 

  11. Boucher TJ, Okuse K, Bennett DL, et al. (2000) Potent analgesic effects of GDNF in neuropathic pain states. Science 290(5489): 124–127

    Article  PubMed  CAS  Google Scholar 

  12. Burgess SE, Gardell LR, Ossipov MH, et al. (2002) Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci 22(12): 5129–5136

    PubMed  CAS  Google Scholar 

  13. Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron 52(1): 77–92

    Article  PubMed  CAS  Google Scholar 

  14. Casula MA, Facer P, Powell AJ, et al. (2004) Expression of the sodium channel beta3 subunit in injured human sensory neurons. Neuroreport 15(10): 1629–1632

    Article  PubMed  CAS  Google Scholar 

  15. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26(1): 13–25

    Article  PubMed  CAS  Google Scholar 

  16. Chabal C, Jacobson L, Mariano A, et al. (1992) The use of oral mexiletine for the treatment of pain after peripheral nerve injury. Anesthesiology 76(4): 513–517

    Article  PubMed  CAS  Google Scholar 

  17. Chabal C, Russell LC, Burchiel KJ (1989) The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 38(3): 333–338

    Article  PubMed  CAS  Google Scholar 

  18. Chiou-Tan FY, Tuel SM, Johnson JC, et al. (1996) Effect of mexiletine on spinal cord injury dysesthetic pain. Am J Phys Med Rehabil 75(2): 84–87

    Article  PubMed  CAS  Google Scholar 

  19. Chung JM, Chung K (2004) Sodium channels and neuropathic pain. Novartis Found Symp 261: 19–27

    Article  PubMed  CAS  Google Scholar 

  20. Coste B, Crest M, Delmas P (2007) Pharmacological dissection and distribution of NaN/Nav1.9, t-type Ca2+ currents, and mechanically activated cation currents in different populations of DRG neurons. J Gen Physiol. 129(1): 57–77

    Article  PubMed  CAS  Google Scholar 

  21. Coste B, Osorio N, Padilla F, et al. (2004) Gating and modulation of presumptive Nav1.9 channels in enteric and spinal sensory neurons. Mol Cell Neurosci 26(1): 123–134

    Article  PubMed  CAS  Google Scholar 

  22. Coward K, Jowett A, Plumpton C, et al. (2001) Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in injured human sensory neurons. Neuroreport 12(3): 483–488

    Article  PubMed  CAS  Google Scholar 

  23. Coward K, Plumpton C, Facer P, et al. (2000) Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states. Pain 85(1–2): 41–50

    Article  PubMed  CAS  Google Scholar 

  24. Craner MJ, Klein JP, Renganathan M, et al. (2002) Changes of sodium channel expression in experimental painful diabetic neuropathy. Ann Neurol 52(6): 786–792

    Article  PubMed  CAS  Google Scholar 

  25. Cummins TR, Dib-Hajj SD, Waxman SG (2004) Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci 24(38): 8232–8236

    Article  PubMed  CAS  Google Scholar 

  26. Dejgard A, Petersen P, Kastrup J (1988) Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1(8575-6): 9–11

    Article  PubMed  CAS  Google Scholar 

  27. Devor M (1991) Neuropathic pain and injured nerve: peripheral mechanisms. Br Med Bull 47(3): 619–630

    PubMed  CAS  Google Scholar 

  28. Devor M, Govrin-Lippmann R, Angelides K (1993) Na+ channel immunolocalization in peripheral mammalian axons and changes following nerve injury and neuroma formation. J Neurosci 13(5): 1976–1992

    PubMed  CAS  Google Scholar 

  29. Devor M, Wall PD, Catalan N (1992) Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 48(2): 261–268

    Article  PubMed  CAS  Google Scholar 

  30. Dib-Hajj SD, Fjell J, Cummins TR, et al. (1999) Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 83(3): 591–600

    Article  PubMed  CAS  Google Scholar 

  31. Dib-Hajj SD, Rush AM, Cummins TR, et al. (2005) Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 128(Pt 8): 1847–1854

    Article  PubMed  CAS  Google Scholar 

  32. Dick IE, Brochu RM, Purohit Y, et al. (2007) Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain 8(4): 315–324

    Article  PubMed  CAS  Google Scholar 

  33. Djouhri L, Fang X, Okuse K, et al. (2003) The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J Physiol 550(Pt 3): 739–752

    Article  PubMed  CAS  Google Scholar 

  34. Dogra S, Beydoun S, Mazzola J, et al. (2005) Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study. Eur J Pain 9(5): 543–554

    Article  PubMed  CAS  Google Scholar 

  35. Ferrante FM, Paggioli J, Cherukuri S, Arthur GR (1996) The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg 82(1): 91–97

    Article  PubMed  CAS  Google Scholar 

  36. Fjell J, Cummins TR, Dib-Hajj SD, et al. (1999) Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons. Brain Res Mol Brain Res 67(2): 267–282

    Article  PubMed  CAS  Google Scholar 

  37. Galer BS, Miller KV, Rowbotham MC (1993) Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology 43(6): 1233–1235

    PubMed  CAS  Google Scholar 

  38. Gammaitoni AR, Alvarez NA, Galer BS (2003) Safety and tolerability of the lidocaïne patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol 43(2): 111–117

    Article  PubMed  CAS  Google Scholar 

  39. Gold MS, Weinreich D, Kim CS, et al. (2003) Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. J Neurosci 23(1): 158–166

    PubMed  CAS  Google Scholar 

  40. Gracely RH, Lynch SA, Bennett GJ (1992) Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51(2): 175–194

    Article  PubMed  CAS  Google Scholar 

  41. Hong S, Morrow TJ, Paulson PE, et al. (2004) Early painful diabetic neuropathy is associated with differential changes in tetrodotoxinsensitive and-resistant sodium channels in dorsal root ganglion neurons in the rat. J Biol Chem 279(28): 29341–29350

    Article  PubMed  CAS  Google Scholar 

  42. Hong S, Wiley JW (2006) Altered expression and function of sodium channels in large DRG neurons and myelinated A-fibers in early diabetic neuropathy in the rat. Biochem Biophys Res Commun 339(2): 652–660

    Article  PubMed  CAS  Google Scholar 

  43. Isom LL (2000) I. Cellular and molecular biology of sodium channel beta-subunits: therapeutic implications for pain? Am J Physiol Gastrointest Liver Physiol 278(3): G349–G353

    PubMed  CAS  Google Scholar 

  44. Isom LL, De Jongh KS, Patton DE, et al. (1992) Primary structure and functional expression of the beta1 subunit of the rat brain sodium channel. Science 256(5058): 839–842

    Article  PubMed  CAS  Google Scholar 

  45. Ji RR, Woolf CJ (2001) Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis 8(1): 1–10

    Article  PubMed  CAS  Google Scholar 

  46. Kajander KC, Bennett GJ (1992) Onset of a painful peripheral neuropathy in rat: a partial and differential deafferentation and spontaneous discharge in A beta and A delta primary afferent neurons. J Neurophysiol 68(3): 734–744

    PubMed  CAS  Google Scholar 

  47. Kalso E, Tramèr MR, McQuay HJ, Moore RA (1998) Systemic local-anaesthetic-type drugs in chronic pain: a systematic review. Eur J Pain 2(1): 3–14

    Article  PubMed  CAS  Google Scholar 

  48. Kastrup J, Petersen P, Dejgaård A, et al. (1987) Intravenous lidocaine infusion: a new treatment of chronic painful diabetic neuropathy? Pain 28(1): 69–75

    Article  PubMed  CAS  Google Scholar 

  49. Kemper CA, Kent G, Burton S, Deresinski SC (1998) Mexiletine for HIV-infected patients with painful peripheral neuropathy: a double blind, placebo-controlled, crossover treatment trial. J Acquir Immune Defic Syndr Hum Retrovirol 19(4): 367–372

    PubMed  CAS  Google Scholar 

  50. Kerr BJ, Souslova V, McMahon SB, Wood JN (2001) A role for the TTX-resistant sodium channel Nav1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport 12(14): 3077–3080

    Article  PubMed  CAS  Google Scholar 

  51. Kieburtz K, Simpson D, Yiannoutsos C, et al. (1998) A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team. Neurology 51(6): 1682–1688

    PubMed  CAS  Google Scholar 

  52. Kim CH, Oh Y, Chung JM, Chung K (2001) The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. Brain Res Mol Brain Res 95(1–2): 153–161

    Article  PubMed  CAS  Google Scholar 

  53. Kral MG, Xiong Z, Study RE (1999) Alteration of Na+ currents in dorsal root ganglion neurons from rats with a painful neuropathy. Pain 81(1–2): 15–24

    Article  PubMed  CAS  Google Scholar 

  54. Krzemien DM, Schaller KL, Levinson SR, Caldwell JH (2000) Immunolocalization of sodium channel isoform NaCh6 in the nervous system. J Comp Neurol 420(1): 70–83

    Article  PubMed  CAS  Google Scholar 

  55. Lai J, Gold MS, Kim CS, et al. (2002) Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, Nav1.8. Pain 95(1–2): 143–152

    Article  PubMed  CAS  Google Scholar 

  56. Leffler A, Cummins TR, Dib-Hajj SD, et al. (2002) GDNF and NGF reverse changes in repriming of TTX-sensitive Na(+) currents following axotomy of dorsal root ganglion neurons. J Neurophysiol 88(2): 650–658

    PubMed  CAS  Google Scholar 

  57. Lyu YS, Park SK, Chung K, Chung JM (2000) Low-dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model. Brain Res 871(1): 98–103

    Article  PubMed  CAS  Google Scholar 

  58. Maingret F, Coste B, Padilla F, et al. (2008) Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol 131(3): 211–225

    Article  PubMed  CAS  Google Scholar 

  59. Mao J, Chen LL (2000) Systemic lidocaïne for neuropathic pain relief. Pain 87(1): 7–17

    Article  PubMed  CAS  Google Scholar 

  60. Nassar MA, Stirling LC, Forlani G, et al. (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci USA 101(34): 12706–12711

    Article  PubMed  CAS  Google Scholar 

  61. Omana-Zapata I, Khabbaz MA, Hunter JC, et al. (1997) Tetrodotoxin inhibits neuropathic ectopic activity in neuromas, dorsal root ganglia and dorsal horn neurons. Pain 72(1–2): 41–49

    Article  PubMed  CAS  Google Scholar 

  62. Padilla F, Couble ML, Coste B, et al. (2007) Expression and localization of the Nav1.9 sodium channel in enteric neurons and in trigeminal sensory endings: implication for intestinal reflex function and orofacial pain. Mol Cell Neurosci 35(1): 138–152

    Article  PubMed  CAS  Google Scholar 

  63. Pertin M, Ji RR, Berta T, et al. (2005) Up regulation of the voltagegated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons. J Neurosci 25(47): 10970–10980

    Article  PubMed  CAS  Google Scholar 

  64. Priest BT, Murphy BA, Lindia JA, et al. (2005) Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Nav1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci USA 102(26): 9382–9387

    Article  PubMed  CAS  Google Scholar 

  65. Renganathan M, Dib-Hajj S, Waxman SG (2002) Na(v)1.5 underlies the “third TTX-R sodium current” in rat small DRG neurons. Brain Res Mol Brain Res 106(1–2): 70–78

    Article  PubMed  CAS  Google Scholar 

  66. Rowbotham MC, Reisner-Keller LA, Fields HL (1991) Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 41(7): 1024–1028

    PubMed  CAS  Google Scholar 

  67. Roy ML, Narahashi T (1992) Differential properties of tetrodotoxinsensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci 12(6): 2104–2111

    PubMed  CAS  Google Scholar 

  68. Roza C, Laird JM, Souslova V, et al. (2003) The tetrodotoxin-resistant Na+ channel Nav1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J Physiol 550(Pt 3): 921–926

    Article  PubMed  CAS  Google Scholar 

  69. Sangameswaran L, Fish LM, Koch BD, et al. (1997) A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J Biol Chem 272(23): 14805–14809

    Article  PubMed  CAS  Google Scholar 

  70. Shah BS, Gonzalez MI, Bramwell S, et al. (2001) Beta3, a novel auxiliary subunit for the voltage gated sodium channel is up regulated in sensory neurones following streptozocin induced diabetic neuropathy in rat. Neurosci Lett. 309(1): 1–4

    Article  PubMed  CAS  Google Scholar 

  71. Shah BS, Stevens EB, Gonzalez MI, et al. (2000) Beta3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is up regulated in the chronic constriction injury model of neuropathic pain. Eur J Neurosci 12(11): 3985–3990

    Article  PubMed  CAS  Google Scholar 

  72. Sindrup SH, Jensen TS (1999) Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 83(3): 389–400

    Article  PubMed  CAS  Google Scholar 

  73. Sleeper AA, Cummins TR, Dib-Hajj SD, et al. (2000) Changes in expression of two tetrodotoxin-resistant sodium channels and their currents in dorsal root ganglion neurons after sciatic nerve injury but not rhizotomy. J Neurosci 20(19): 7279–7289

    PubMed  CAS  Google Scholar 

  74. Takahashi N, Kikuchi S, Dai Y, et al. (2003) Expression of auxiliary beta subunits of sodium channels in primary afferent neurons and the effect of nerve injury. Neuroscience 121(2): 441–450

    Article  PubMed  CAS  Google Scholar 

  75. Veneroni O, Maj R, Calabresi M, et al. (2003) Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain. Pain 102(1–2): 17–25

    Article  PubMed  CAS  Google Scholar 

  76. Wall PD, Devor M (1983) Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 17(4): 321–339

    Article  PubMed  CAS  Google Scholar 

  77. Wang R, Guo W, Ossipov MH, et al. (2003) Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain. Neuroscience 121(3): 815–824

    Article  PubMed  CAS  Google Scholar 

  78. Waxman SG, Kocsis JD, Black JA (1994) Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is re-expressed following axotomy. J Neurophysiol 72(1): 466–470

    PubMed  CAS  Google Scholar 

  79. West JW, Patton DE, Scheuer T, et al. (1992) A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci USA 89(22): 10910–10914

    Article  PubMed  CAS  Google Scholar 

  80. Wu G, Ringkamp M, Murinson BB, et al. (2002) Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J Neurosci 22(17): 7746–7753

    PubMed  CAS  Google Scholar 

  81. Xiao HS, Huang QH, Zhang FX, et al. (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci USA 99(12): 8360–8365

    Article  PubMed  CAS  Google Scholar 

  82. Yang Y, Wang Y, Li S, et al. (2004) Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 41(3): 171–174

    Article  PubMed  CAS  Google Scholar 

  83. Yashpal K, Pitcher GM, Parent A, et al. (1995) Noxious thermal and chemical stimulation induce increases in 3H-phorbol 12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C. J Neurosci 15(5 Pt 1): 3263–3272

    PubMed  CAS  Google Scholar 

  84. Yu FH, Westenbroek RE, Silos-Santiago I, et al. (2003) Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci 23(20): 7577–7585

    PubMed  CAS  Google Scholar 

  85. Zhang XF, Zhu CZ, Thimmapaya R, et al. (2004) Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury. Brain Res 1009(1–2): 147–158

    Article  PubMed  CAS  Google Scholar 

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  1. faculté de médecine, CRN2M, CNRS-UMR 6231, boulevard Pierre-Dramard, 13916, Marseille cedex 20, France

    F. Maingret & P. Delmas

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Maingret, F., Delmas, P. Rôle des canaux sodium des neurones afférents primaires dans les douleurs neuropathiques périphériques. Douleur analg 21, 194–202 (2008). https://doi.org/10.1007/s11724-008-0107-2

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