Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Antiépileptiques et canaux ioniques

  • 34 Accesses


Les antiépileptiques sont utilisés de manière empirique dans le traitement des douleurs neuropathiques. Si certains d’entre eux affectent la neurotransmission glutamatergique (acide valproïque, felbamate) ou GABAergique (benzodiazépines, vigabatrin), leurs cibles principales sont les canaux sodium (phénytoïne, carbamazépine, lamotrigine, acide valproïque, felbamate) et calcium (gabapentin) sensibles au potentiel. Chez l’animal, les effets antihyperalgésiques des antiépileptiques peuvent être mis en évidence dans des modèles de douleurs non seulement neuropathiques mais aussi inflamamtoires. Les modifications marquées de l’expression et/ou des propriétés des cibles des antiépileptiques observées dans ces modèles altèrent les propriétés élecriques des membranes des neurones, ce qui pourrait contribuer à la genèse des douleurs. C’est le cas plus particulièrement des changements des caractéristiques des canaux sodium sensibles au potentiel, dont certains sont experimés de manière préférentielle, voire speércifique, dans les fibres afférentes primaires qui transmettent les messages nociceptifs. On peut penser que des composés synthétisés pour moduler sélectivement les canaux ioniques propres aux fibres afférentes primaires auront une efficacié thérapeutique supérieure à celle des antiépileptiques actuellement disponibles, tout en étant dépourvus de leurs efets indśirables.


Anticonvulsant drugs are empirically used for alleviating neuropathic pain. Although some of them affect glutamatergic (valproic acid, felbamate) and GABAergic (benzodiazepines, vigabatrin) neurotransmission, their main targets are voltage-dependent sodium (phenytoin, carbamazepne, lamotrigine, valproic acid, felbamate) and calcium (gabapentin) channels. Anticonvulsant drugs exhibit antihyperalgesic effects in animal models of both neuropathic and inflammatory pain. Marked alterations of the expression and/or the properties of anticonvulsants’ targets in these animal models change the electrical properties of the neurone membranes, and might contribute to the generation and maintenance of pain. This applies particularly to the modifications of the characteristics of the voltage-dependent sodium channels, some of which are preferentially, and even specifically, expressed in primary afferent fibres that convey nociceptive messages.Compounds developed to selectively modulate the ionic channels proper to the primary afferent fibres can be expected to have higher therapeutic efficacy than anticonvulsant drugs presently available, and to be devoid of their undesirable effects.

This is a preview of subscription content, log in to check access.


  1. 1.

    Abulan F.S., Dhariwal M.A.H., Al-Bekairi A.M. andRaza M.: Antinociceptive activity of sodium valproate in mice after chronic treatment.Gen. Pharmacol. 29, 463–467, 1997.

  2. 2.

    Akopian A.N., Sivilotti L. andWood J.N.: A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.Nature 379, 257–262, 1996.

  3. 3.

    Arbuckle J.B. andDocherty R.J.: Expression of tetrodotoxin-resistant sodium channels in capsaicin-sensitive dorsal root granglion neurons a dults rats.Neurosci. Lett. 185, 70–73, 1995.

  4. 4.

    Bennett G.J. andXie Y.K.: A peripheral mononeuropathy in rat produces disorders of pain sensation like those seen in man.Pain 33, 87–107, 1988.

  5. 5.

    Bianchi M., Rossoni G., Sacerdote P., Panerai A.E. andBerti F.: Carbamazepine exerts anti-inflammatory effects in the rat..Eur. J. Pharmacol. 294, 71–74, 1995.

  6. 6.

    Black J.A., Dib-Hajj S., McNabola K., Jeste S., Rizzo M.A., Kocsis J.D. andWaxman S.G.: Spinal sensory neurons express multiple sodium channel a-subunit mRNAs.Mol. Brain Res. 43, 117–132. 1996.

  7. 7.

    Black J.A. andWaxman S.G.: Sodium channels expression: a dynamic process in neurones and non-neuronal cells.Dev. Neurosci. 18, 139–152, 1996.

  8. 8.

    Black J.A., Yokayama S., Higashida H., Ranson B.R. andWaxman S.G.: Sodium channel mRNAs I, II and III in the CNS: cell-specific expression.Mol. Brain Res. 22, 275–289, 1994.

  9. 9.

    Blackburn-Munro G. andFleetwood-Walker S.M.: The effect of Na+ channel blockers on somatosensory processing by rat dorsal horn neurones.Neuroreport 8, 1549–1554, 1997.

  10. 10.

    Bossu J.L. andFeltz A.: Patch-clamp study of the tetrodotoxin-resistant sodium current in group C sensory neurnes.Neurosci. Lett. 51, 241–246, 1984.

  11. 11.

    Bowersox S.S., Gadbois T., Singh T., Pettus M., Wang Y.X. andLuther R.R.: Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinocicpetion in rat models of acute, persistent and neuropathic pain.J. Pharmacol. Exp. Ther. 279, 1243–1249, 1996.

  12. 12.

    Brose W.G., Gutlove D.P., Bowersox S.S. andMcGuire D.: Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain.Clin. J. Pain 13, 256–259, 1997.

  13. 13.

    Burchiel K.J.: Carbamazepine inhibits spontaneous activity in experimental neuromas.Exp. Neurol. 102, 249–253, 1988.

  14. 14.

    Caffrey J.M., Eng D.L., Black J.A., Waxman S.G. andKocsis J.D.: Three types of sodium channels in adult rat dorsal root ganglion neurons.Brain Res. 592, 283–297, 1992.

  15. 15.

    Calcutt N.A. andChaplan S.R.: Spinal pharmacology of tactile allodynia in diabetic rats.Br. J. Pharmacol. 122, 1478–1482, 1997.

  16. 16.

    Carlton S.M. andZhou S.: Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin.Pain 76, 201–207, 1998.

  17. 17.

    Castro-Lopes J.M., Malcangio M., Pan B. andBowery N.G.: Complex changes of GABAA and GABAB receptor binding in the spinal cord dorsal horn following peripheral inflammation or neurectomy.Brain Res. 679, 289–297, 1995.

  18. 18.

    Castro-Lopes J.M., Tavares I. andCoimbra A.: GABA decreases in the spinal cord dorsal horn after peripheral neurectomy.Brain Res. 620, 287–291, 1993.

  19. 19.

    Castro-Lopes J.M., Tavares I., Tölle T.R. andCoimbra A.: Carrageenan-induced inflammation of the hind foot provokes a rise of GABA-immunoreactive cells in the rat spinal cord that is prevented by peripheral neurectomy or neonatal capsaicin treatment.Pain 56, 193–201, 1994.

  20. 20.

    Castro-Lopes J.M., Tavares I., Tölle T.R., Coito A. andCoimbra A.: Increase in GABAergic cells and GABA levels in the spinal cord in unilateral inflammation of the hindlimb in the rat.Eur. J. Neurosci. 4, 296–301, 1992.

  21. 21.

    Castro-Lopes J.M., Tölle T.R., Pan B. andZieglgänsberger W.: Expression of GAD mRNA in spinal cord neurons of normal and monoarthritic rat.Mol. Brain Res. 26, 169–176, 1994.

  22. 22.

    Catterall W.A.: Cellular and molecular biology of voltage-gated sodium channels.Physiol. Rev. 72, (suppl 4), S15-S48, 1992.

  23. 23.

    Cesare P. andMcNaughton P.: Peripheral pain mechanisms.Curr. Opin. Neurobiol. 7, 493–499, 1996.

  24. 24.

    Chaplan S.R., Pogrel J.W. andYaksh T.L.: Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia.J. Pharmacol. Exp. Ther. 269, 1117–1123, 1994.

  25. 25.

    Chapman A.G., Meldrum B.S. andMendes E.: Acute anticonvulsivant activity of structural analogues of valproic acid and changes in brain GABA and asparte content.Life Sci. 32, 2023–2031, 1983.

  26. 26.

    Chapman V. andDickenson A.H.: Inflmamation reveals inhibition of noxious responses of rat spinal neurones by carbamazepine.Neuroreport 8, 1399–1404, 1997.

  27. 27.

    Chapman V., Suzuki R., Chamarette H.L.C., Rygh L.J. andDickenson A.H.: Effects of systemic carbamazepine and gabapentin on spinal neuronal response sin spinal nerve ligated rats.Pain 75, 261–272, 1998.

  28. 28.

    Chen J., Ikeda S.R., Lang W., Isales C.M. andWei X.: Molecular cloning of a putative tetrodotoxin-resistant sodium channel from dog nodose ganglion neurons.Gene 202, 7–14, 1997.

  29. 29.

    Cheung H., Kamp D. andHarris E.: An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels.Epilepsy Res. 13, 107–112, 1992.

  30. 30.

    Coderre T.J.: Contribution of protein kinase C to central sensitization and persistent pain following tissue injury.Neurosci. Lett. 140, 181–184, 1992.

  31. 31.

    Coderre T.J., Jatz J., Vaccarino A.L. andMelzack R.: Contribution of central plasticity to pathological pain: review of clinical and expermental evidence.Pain 52, 258–285, 1993.

  32. 32.

    Coderre T.J. andMelzack R.: The role of NMDA receptor-operated calcium channels in persistent nociception after formalin-induced tissue injury.J. Neurosci. 12, 3671–3675, 1992.

  33. 33.

    Crawford M.E., Jensen F.M., Toftdahl D.B. andMadsen J.B.: Direct spinal effect of intrathecal and extradural midazolam on visceral noxious stimulation in rabbits.Br. J. Pharmacol. 70, 642–646, 1993.

  34. 34.

    Cummins T.R. andWaxmam S.G.: Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury.J. Neurosci. 17, 3503–3514, 1997.

  35. 35.

    DeSarro G., Ongini E., Bertorelli R., Aguglia U. andDeSarro A.: Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors involved in the anticonvulsivant activity of felbamate in DBA/2 mice.Eur. J. Pharmacol. 262, 11–19, 1994.

  36. 36.

    Devor M.: The pathophysiology of damaged peripheral nerves.In Wall P.D., Melzack R. (Eds.),Textbook of Pain, 3rd ed., Churchill-Livingstone, Edimburgh, 1994, pp. 79–100.

  37. 37.

    Diaz A. andDickenson A.H.: Blockade of spinal N- and P-type, but not L-type, calcium channels inhibits the excitability of rat dorsal horn neurones produced by subcutaneous formalin inflammation.Pain 69, 93–100, 1997.

  38. 38.

    Dib-Hajj S.D., Black J.A., Cummins T.R., Kenney A.M., Kocsis J.D. andWaxman S.G.: Rescue of alpha-SNS sodium channel expession in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo.J. Neurophysiol. 79, 2668–2676, 1998.

  39. 39.

    Dib-Hajj S.D., Black J.A., Felts P. andWaxman S.G.: Down-regulation of transcripts for Na channel a-SNS in spinal sensory neurons following axotomy.Proc. Natl. Acad. Sci. USA 93, 14950–14954, 1996.

  40. 40.

    Dib-Hajj S.D., Tyrrell L., Black J.A. andWaxman S.G.: NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy.Proc. Natl. Acad. Sci. USA 95, 8963–8968, 1998.

  41. 41.

    Dietrich P.S., McGivern J.G., Delgado S.G., Koch B.D., Eglen R.M., Hunter J.C. andSangameswaean L.: Functional analyssi of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.J. Neurochem. 70, 2262–2272, 1998.

  42. 42.

    Dray A., Urban L. andDickenson A.: Pharmacology of chronic pain.Trends Pharmacol. Sci. 15, 190–197, 1994.

  43. 43.

    Dubner R. andRuda M.A.: Activity-dependent neuronal plasticity following tissue injury and inflammation.Trends Neurosci. 3, 96–103, 1992.

  44. 44.

    Eccles J.C.:The Physiology of Synapses. Springer Verlag, Berlin, Göttingen, Heidelberg, 1964.

  45. 45.

    Elliott A.A. andElliott J.R.: Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adulte rat dorsal root gangla.J. Physiol. (Lond.),463, 39–56, 1993.

  46. 46.

    England S., Bevan S. andDocherty R.J.: PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade.J. Physiol. (Lond.),495, 429–440, 1996.

  47. 47.

    Everill B., Rizzo M.A. andKocsis J.D.: Morphologically identified cutaneous afferent DRG neurons express three different potassium currents in varying proportions.J. Neurophysiol. 79, 1814–1824, 1998.

  48. 48.

    Field M.J., Holloman E.F., McCleary S., Hughes J. andSingh L.: Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain.J. Pharmacol. Exp. Ther. 282, 1242–1246, 1997.

  49. 49.

    Field M.J., Oles R.J., Lewis A.S., McCleary S., Hughes J. andSingh L.: Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents.Br. J. Pharmacol. 21, 1513–1522, 1997.

  50. 50.

    Gardenas C.G., Del Mar L.P., Cooper B.Y. andScroggs R.S.: 5HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons.J. Neurosci. 17, 7181–7189, 1997.

  51. 51.

    Gee N.S., Brown J.P., Dissanayake V.U.K., Offord J., Thurlow R. andWoodruff G.N.: The novel anticonvulsivant drug, gabapentin (neurontin), binds to the a2∂ subunit of a calcium channel.J. Biol. Chem. 271, 5768–5776, 1996.

  52. 52.

    Gillin S. andSorkin L.S.: Gabapentin reverses the allodynia produced by the administration of anti-GD2 ganglioside, an immunotherapeutic durg.Anest,. Analg. 86, 111–116, 1998.

  53. 53.

    Gohil K., Bell J.R., Ramachandran J. andMiljanich G.P.: Neuroanatomical distribution of receptors for a novel voltage sensitive calcium channel antagonist, SNX-230 (w-conopeptide MVIIC).Brain Res. 653, 258–266, 1994.

  54. 54.

    GoldM.S., Reichling D.B., Shuster M.J. andLevine J.D.: Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors.Proc. Natl. Acad. Sci. USA, 93, 1108–1112, 1996.

  55. 55.

    Gurnett C.A., de Waard M. andCampbell K.P.: Dual function of the voltage-dependent Ca2+ channel a2∂ subunit in current stimulation and subunit interaction.Neuron 16, 431–440, 1996.

  56. 56.

    Hammond D.L.: Inhibitory neurotransmitters and nociception: role of GABA and glycine.In: Dickenson A., Besson J.M. (Eds), Handbook of Experimental Pharmacology, Vol. 130,The Pharmacology of Pain, Springer-Verlag, Berlin, Heidelberg, 1997, pp. 361–383.

  57. 57.

    Hofmann F., Biel M. andFlockerzi V.: Molecular basis for Ca2+ channel diversity.Annu. Rev. Neurosci. 17, 399–418, 1994.

  58. 58.

    Hökfelt T., Zhang X. andWiesenfeld-Hallin Z.: Messenger plasticity in primary sensory neurons following axotomy and its functional implications.Trends Neurosci. 17, 22–30, 1994.

  59. 59.

    Houghton A.K., Lu Y. andWetstlund K.N.: S-(+)-3-isobutylgaba and its stereoisomer reduces the amount of inflammation and hyperalgesia in an acute arthritis model in the rat.J. Pharmacol. Exp. Ther. 285, 533–538, 1998.

  60. 60.

    Hunter J.C., Gogas K.R., Hedley L.R., Jacobson L.O., Kassotakis L., Thompson J. andFontana D.J.: The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain.Eur. J. Pharmacol. 324, 153–160, 1997.

  61. 61.

    Hwang J.H. andYaksh T.L.: Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat.Reg. Anesth. 22, 249–256, 1997.

  62. 62.

    Iadarola M.J., Raines A. andGale K.: Differential effects of n-dipropylacetate and amino-oxyacetic acid on g-aminobutyric levels in discrete areas of rat brain.J. Neurochem. 33, 1119–1123, 1979.

  63. 63.

    Ibuki T., Hama A.T., Wang X.T., Pappas G.D. andSagen J.: Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts.Neuroscience 76, 845–858, 1997.

  64. 64.

    Imamura Y. andBennett G.J.: Felbamate relieves several abnormal pain sensations in rats with an experimental peripheral neuropathy.J. Pharmacol. Exp. Ther. 275, 177–182, 1995.

  65. 65.

    Jeftinija S.: The role of tetrodotoxin-resistant sodium channels of small primary afferent fibers.Brain Res. 639, 125–134, 1994.

  66. 66.

    Johnston G.: GABAA receptor pharmacology.Pharmacol. Ther. 69, 173–198, 1996.

  67. 67.

    Jun J.H. andYaksh T.L.: The effect of intrathecal gabapentin and 3-isobutyl g-aminobutiric acid on the hyperalgesia observed after thermal injury in the rat.Anesth. Analg. 86, 348–354, 1998.

  68. 68.

    Kelly K.M., Gross R.A. andMacdonald R.L.: Valproic acid selectively reduces the low-thrreshold (T) calcium current in rat nodose neurons.Neurosci. Lett. 116, 233–238, 1990.

  69. 69.

    Ker L.M., Filloux F., Olivera B.M., Jackson H. andWamsley J.K.: Autoradiographic localization of calcium channels with [125I]w-conotoxin in the rat brain.Eur. J. Pharmacol. 146, 181–183, 1988.

  70. 70.

    Kim S.H. andChung J.M.: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat.Pain 50, 355–363, 1992.

  71. 71.

    Kuo C.C., Chen R.S., Lu L. andChen R.C.: Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytion and possible therapeutic implications.Mol. Pharmacol. 51, 1077–1083, 1997.

  72. 72.

    Leach M.J., Marden C.M. andMiller A.A.: Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action.Epilepsia 27, 490–497, 1986.

  73. 73.

    Lees G. andLeach M.J.: Studies on the mechanism of action of the novel anticonvulsivant lamotrigine (Lamictal) using primary neuroglial cultures from rat cortex.Brain Res. 612, 190–199, 1993.

  74. 74.

    Lippert B., Metcalf B.W., Jung M.J. andCasara P.: 4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain.Eur. J. Biochem. 74, 441–445, 1977.

  75. 75.

    Loscher W. andVetter M.: In vivo effects of aminooxyacetic acid and valproic acid on nerve terminals (synaptosomal) GABA levels in discrete brain areas of the rat. Correlation to pharmacological activities. Biochem.Pharmacol. 34, 1747–1756, 1985.

  76. 76.

    Luger T.J., Hayashi T., Lorenz I.H. andHill H.F.: Mechanisms of the influence of midazolam on morphine antinociception at spinal and supraspinal levels in rats.Eur. J. Pharmacol. 271, 421–431, 1994.

  77. 77.

    Macdonald R.L.: Cellular effects of antiepileptic drugs.In: Engel J. Pedley T.A. (Eds),Epilepsy: A Comprehensive Textbook, Lippincott-Raven Publishers, Philadelphia, 1997, pp. 1383–1391.

  78. 78.

    Malmberg A.B., Brandon E.P., Idzerda R.L., Liu H. andMcKnight G.S., Basbaum A.I.: Diminished inflammation and nociceptive pain with predervation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase.J. Neurosci. 17, 7462–7470, 1997.

  79. 79.

    Malmberg A.B., Chen C., Tonegawa S. andBasbaum A.I.: Preserved acute pain and reduced neuropathic pain in mice lacking PKCg.Science 278, 279–283, 1997.

  80. 80.

    Malmberg A.B. andYaksh T.L.: Voltage-sensitive calcium channels in spinal nociceptive processing. Blocade of N- and P-type cahnnels inhibits formalin-induced nociception.J. Neurosci. 14, 4882–4890, 1994.

  81. 81.

    Matzer O. andDevor M.: Na+ conductance and the threshold for repetitive neuronal firing.Brain Res. 597, 92–98, 1992.

  82. 82.

    Matzer O. andDevor M.: Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels.J. Neurophysiol. 72, 349–359, 1994.

  83. 83.

    McCabe R.T., Sofia R.D., Layer R.T., Leiner K.A., Faull R.L.M., Narang N. andWamsley J.K.: Felbamate increases [3H]glycine binding in rat brain and sections of human postmortem brain.J. Pharmacol. Exp. Ther. 286, 991–999, 1988.

  84. 84.

    McCabe R.T., Wasterlain C.G., Kucharczyk N., Sofia R.D. andVogel J.R.: Evidence for anticonvulsivant and neuroprotective action of felbamate mediated by strychnine-insensitive glycine receptors.J. Pharmacol. Exp. Ther. 264, 1248–1252, 1993.

  85. 85.

    McLean M.J. andMacdonald R.L.: Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potential in mouse central neurons in cell culture.J. Pharmacol. Exp. Ther. 237, 1001–1011, 1986.

  86. 86.

    Meller S.T., Dykstra C. andGebhart G.F.: Acute thermal hyperalgesia in the rat is produced by activation of N-methyl-D-aspartate receptors and protein kinase C and production of nitric oxide.Neuroscience 71, 327–335, 1996.

  87. 87.

    Miljanich G.P. andRamachandran J.: Antagonists of neuronal calcium channels: structure, fonction, and therapeutic implications.Annu. Rev. Pharmacol. Toxicol. 35, 707–735, 1995.

  88. 88.

    Munglani R. andHunt S.P.: Molecular biolgoy of pain.Br. J. Anaesth. 75, 186–192, 1995.

  89. 89.

    Nahin R.L. andHylden J.L.K.: Peripheral inflammation is associated with increased glutamic acid decarboxylase immunoreactivity in the rat spinal cord.Neurosci. Lett. 128, 226–230, 1991.

  90. 90.

    Nakamura-Craig M. andFollenfant R.L.: Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and in the chronic hyperalgesia in rats with streptozotocin-induced diabetes.Pain 63, 33–37, 1995.

  91. 91.

    Nebe J., Vanegas H. andSchaible H.G.: Spinal application of w-conotoxin GVIA, an N-type calcium channel antagonist, attenuates enhancement of dorsal spinal neuronal responses caused by intra-articular injection of mustard oil in the rat.Exp. Brain Res. 120, 61–69, 1998.

  92. 92.

    Neugebauer V., Vanegas H., Nebe J., Rümenapp P andSchaible H.G.: Effects of N- and L-type calcium channel antagonists on the responses of nociceptive spinal cord neurons to mechanical stimulation of the normal and inflamed knee joint.J. Neurophysiol. 75, 3740–3749, 1996.

  93. 93.

    Novakovic S.D., Tzoumaka E., McGivern J.G., Haraguchi M., Sangameswaran L., Gogas K.R., Eglen R.M. andHunter J.C.: Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions.J. Neurosci. 18, 2174–2187, 1998.

  94. 94.

    Oaklander A.L. andBelzberg A.J.: Unilateral nerve injury downregulates mRNA for Na+ channel SCN10A bilaterally in rat dorsal root ganglia.Mol. Brain Res. 52, 162–165, 1997.

  95. 95.

    Oh Y., Sashihara S. andWaxman S.G.: In situ hybridation localization of the Na+ channel b1 subunit mRNA in rat CNS neurons.Neurosci. Lett. 176, 119–122, 1994.

  96. 96.

    Olivera B.M., Miljanich G.P., Ramchandran J. andAdams M.E.: Calcium channel diversity and neurotransmitter release: The w-conotoxins and w-agatoxins.Annu. Rev. Biochem. 63, 823–867, 1994.

  97. 97.

    Omote K., Iwasaki H., Kawamata M., Satoh O. andNamiki A.: Effects of verapamil on spinal anesthesia with local anesthetics.Anesth. Analg. 80, 444–448, 1995.

  98. 98.

    Omote K., Sonoda H., Kawamata M., Iwasaki H. andNamiki A.: Potentiation of antinociceptive effects of morphine by calcium channel blockers at the level of the spinal cord.Anesthesiology 79, 746–752, 1993.

  99. 99.

    Oyelese A.A., Rizzo M.A., Waxman S.G. andKocsis J.D.: Differential effects of NGF and BDNF on axotomy-induced changes in GABAA-receptor-mediated conductance and sodium currents in cutaneous afferent neurons.J. Neurophysiol. 78, 31–42, 1997.

  100. 100.

    Partridge B.J., Chaplan S.R., Sakamoto E. andYaksh T.L.: Characterization of the effects of gabapenting and 3-isobutyl-g-aminobutyric acid on substance P-induced thermal hyperalgesia.Anesthesiology 88, 196–205, 1998.

  101. 101.

    Petroff O.A. andRothman D.L.: Measuring human brain GABA in vivo: effects of GABA-transaminase inhibition by vigabatrin.Mol. Neurobiol. 16, 97–121, 1998.

  102. 102.

    Rho J.M., Donevan S.D. andRogawski M.A.: Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate.J. Pharmacol. Exp. Ther. 280, 1383–1391, 1997.

  103. 103.

    Rho J.M., Donevan S.D. andRogawski M.A.: Mechanism of action of the anticonvulsivant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors.Ann. Neurol. 35, 229–234, 1994.

  104. 104.

    Rizzo M.A., Kocsis J.D. andWaxman S.G.: Selective loss of slow and enhancement of fast Na+ currents in cutaneous afferent dorsal root ganglion neurons following axotomy.Neurobiol. Dis. 2, 87–96, 1995.

  105. 105.

    Rizzo M.A., Kocsis J.D. andWaxman S.G.: Mechanisls of paresthesiae, dysesthesiae, and hyperesthesiae: role of Na+ channel heterogeneity.Eur. Neurol. 36, 3–12, 1996.

  106. 106.

    Rock D.M., Kelly K.M. andMacdonald R.L.: Gabapentin actions on ligand- and voltage gated responses in cultured rodent neurons.Epilepsy Res. 16, 89–98, 1993.

  107. 107.

    Rush A.M. andElliott J.R.: Phenytoin and carbamazepine: differential inhibition of sodium currents in small cells from adult rat dorsal root ganglia.Neurosci. Lett. 226, 95–98, 1997.

  108. 108.

    Russell L.C. andBurchiel K.J.: Spontaneous activity in afferent and efferent fibers after chronic axotomy: response to potassium channel blockade.Somatosens. Mot. Res. 6, 163–177, 1998.

  109. 109.

    Safronov B.V., Wolff M. andVogel W.: Functional distribution of three types of Na+ channel on soma and processes of dorsal horn neurones of rat spinal cord.J. Physiol. (Lond.),503, 371–385, 1997.

  110. 110.

    Sangameswaran L., Delgado S.G., Fish L.M., Koch B.D., Jakeman L.B., Stewart G.R., Sze P., Hunter J.C. andHerman R.C.: Structure and function of a novel voltage-gated tetrodotoxin-resistant sodium channel specific to sensory neurons.J. Biol. Chem. 271, 5953–5956, 1996.

  111. 111.

    Sangameswaran L., Fish L.M., Koch B.D., Rabert D.K., Delgado S.G., IIInicka M., Jakeman L.B., Novakovic S., Wong K., Sze P., Tzoumaka E., Stewart G.R., Herman R.C., Chan H., Eglen R.M. andHunter J.C.: A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia.J. Biol. Chem. 272, 14805–14809, 1997.

  112. 112.

    Schechter P.J., Trainer T. andGrove J.: effect of n-dipropylacetate and amino acid concentrations in mouse brain: correlations with anticonvulsivant activity.J. Neurochem. 31, 1325–1327, 1978.

  113. 113.

    Schumacher T.B., Beck H., Steinhäuser C., Schramm J. andElger C.E.: Effects of phenytoin, carbamazepine, and gabapentin on calcium channels in hippocampal granule cells from patients with temporal epilepsy.Epilepsia 39, 355–363, 1998.

  114. 114.

    Shimoyama N., Shimoyama M., Davis A.M., Inturrisi C.E. andElliott K.J.: Spinal gabapentin is antiociceptive in the rat formalin test.Neurosci. Lett. 222, 65–67, 1997.

  115. 115.

    Singh L., Field M.J., Ferris P., Hunter J.C., Oles R.J., Williams R.G. andWoodruff G.N.: The antiepileptic agent gabapentin (Neurotin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine.Psychopharmacology 127, 1–9, 1996.

  116. 116.

    Smith G.D., Harrison S.M., Birch P.J., Elliott P.J., Malcangio M. andBowery N.G.: Increased sensitivity to the antinociceptive activity of (±) baclofen in an animal model of chronic neuropathic, but not chronic inflammatory hyperalgesia.Neuropharmacology 33, 1103–1108, 1994.

  117. 117.

    Song J.H., Nagata K., Huang C.S., Yeh J.Z. andNarahashi T.: Differential block of two types of sodium channels by anticonvulsivants.Neuroreport 7, 3031–3036, 1996.

  118. 118.

    Stanfa C.L., Singh L., Williams R.G. andDickenson A.H.: Gabapentin, ineffective in normal rats, markedly reduces C-fibre evoked responses after inflammation.Neuroreport 8, 587–590, 1997.

  119. 119.

    Stefani A., Spadoni F. andBernardi G.: Gapabentin inhibits calcium currents in rat brain neurons.Neuropharmacology 37, 83–91, 1998.

  120. 120.

    Takemura M., Kiyama H., Fukui H., Tohyama M. andWada H.: Autoradiographic visualization in rat brain of receptors for w-conotoxin GVIA, a newly discovered calcium antagonist.Brain Res. 45, 386–389, 1988.

  121. 121.

    Tanaka M., Cummins T.R., Ishikawa K., Dibhajj S.D., Black J.A. andWaxman S.G.: SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model.Neuroreport 9, 967–972, 1998.

  122. 122.

    Teoh H., Fowler L.J. andBowery N.G.: Effect of lamotrigine on the electrically-evoked release of endogenous amino acids from slices of dorsal horn of the rat spinal cord.Neuropharmacology 34, 1273–1278, 1997.

  123. 123.

    Todorovic S.M. andLingle C.: Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsivant and anesthetic agents.J. Neurophysiol. 79, 240–252, 1998.

  124. 124.

    Toledo-Aral J.J., Moss B.L., He Z.J., Koszowski A.G., Whisenand T., Levinson S.R., Wolf J.J., Silos-Santiago I., Halegoua S. andMandel G.: Identification of PN1, a predominent voltage-dependent sodium channel expressed principally in peripheral neurons.Proc. Natl. Acad. Sci. USA94, 1527–1532, 1997.

  125. 125.

    Trezise D.J., John V.H. andXie X.M.: Voltage- and use-dependent inhibition of Na+ channels in rat sensory neurones by 4030W92, a new antihyperalgesic agent.Br. J. Pharmacol. 124, 953–963, 1998.

  126. 126.

    Van Dongen A.M.J., Van Erp M.G. andVoskuyl R.A.: Valproate reduces excitability by blockade of sodium and potassium channels.Epilepsia 27, 177–182, 1986.

  127. 127.

    Wang S.J., Huang C.C., Hsu K.S., Tsai J.J. andGean P.W.: Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones.Neuroreport 7, 3037–3040, 1996.

  128. 128.

    Waxman S.G., Kocsis J.D. andBlack J.A.: Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reexpressed folowing axotomy.J. Neurophysiol. 72, 466–470, 1994.

  129. 129.

    White H.S., Wolf H.H., Swinyard E.A., Skeen G.A. andSofia R.D.: A neuropharmacologic evaluation of felbamate as a novel anticonvulsivant.Epilepsia 33, 564–272, 1992.

  130. 130.

    Willow M., Kuenzel E.A. andCatterall W.A.: Inhibition of voltagesensitive sodium channels in neuroblastome cells and synaptosomes by the anticonvulsivant drug diphenylhydantoin and carbamazepine.Mol. Pharmacol. 25, 228–234, 1984.

  131. 131.

    Xiao W.H. andBennett G.J.: Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pain in rats.J. Pharmacol. Exp. Ther. 274, 666–672, 19995.

  132. 132.

    Xiao W.H. andBennett G.J.: Gapentin relieves abnormal pain sensation via a spinal site of action in a rat model of painful peripheral neuropathy.Analgesia 2, 267–273, 1996.

  133. 133.

    Xie X., Lancaster B., Peakman T. andGarthwaite J.: Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA channels and with native Na+ channels in rat hippocampal neurones.Pflugers Arch. 430, 437–446, 1995.

  134. 134.

    Yaari Y. andDevor M.: Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas.Neurosci. Lett. 58, 117–122, 1985.

  135. 135.

    Yamamoto T. andSakashita Y.: Differential effects of intrathecally administered N- and P-type voltage-sensitive calcium channel blockers upon two models of experimental mononeuropathy in the rat.Brain Res. 794, 329–332, 1998.

  136. 136.

    Yoshimura N. andde Groat W.C.: Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury.J. Physiol. (Lond.),503, 269–276, 1997.

  137. 137.

    Yoshimura N., White G., Weight F.F. andde Groat W.C.: Different types of Na+ and A-type K+ currents in dorsal root ganglion neurones innervating the rat urinary bladder.J. Physiol. (Lond.),494, 1–16, 1996.

  138. 138.

    Zhang J.M., Donnelly D.F., Song X.J. andLaMotte R.H.: Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons.J. Neurophysiol. 78, 2790–2794, 1997.

  139. 139.

    Zona C., Tancredi V., Palma E., Pirrone G.C. andAvoli M.: Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine.Can. J. Phsyiol. Pharmacol. 68, 545–547, 1990.

Download references

Author information

Correspondence to E. Collin.

Additional information

Texte présenté d’un cours de perfectionnement, intitulé «Douleur et Canaux loniques»qui s’est tenu dans le cadre de la 22e réunion annuelle de la SFD, le 19 novembre 1998 à Versailles.

About this article

Cite this article

Collin, E. Antiépileptiques et canaux ioniques. Doul. et Analg. 12, 219–230 (1999).

Download citation

Key words

  • Anti-épileptiques
  • canaux ioniques
  • douleurs neuropathiques