The role of sodium channels in neuropathic pain

Rogers, Marc; Tang, Lam; Madge, David J.; Stevens, Edward B.

doi:10.1016/j.semcdb.2006.10.009

Cited by 124 publications

(98 citation statements)

References 131 publications

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“…These include such treatments as topical creams (for example, lidocaine), anticonvulsants, and tricyclic antidepressants (reviewed in Rogers et al, 2006).…”

Section: Potential Mechanisms Of Modulation Of Sodium Channel Expressmentioning

confidence: 99%

Neurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states

Wilson-Gerwing

Stucky

McComb

et al. 2008

Experimental Neurology

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Neuropathic pain resulting from chronic constriction injury (CCI) is critically linked to sensitization of peripheral nociceptors. Voltage gated sodium channels are major contributors to this state and their expression can be upregulated by nerve growth factor (NGF). We have previously demonstrated that neurotrophin-3 (NT-3) acts antagonistically to NGF in modulation of aspects of CCI-induced changes in trkA-associated nociceptor phenotype and thermal hyperalgesia. Thus, we hypothesized that exposure of neurons to increased levels of NT-3 would reduce expression of Na v 1.8 and Na v 1.9 in DRG neurons subject to CCI. In adult male rats, Na v 1.8 and Na v 1.9 mRNAs are expressed at high levels in predominantly small to medium size neurons. One week following CCI, there is reduced incidence of neurons expressing detectable Na v 1.8 and Na v 1.9 mRNA, but without a significant decline in mean level of neuronal expression, and similar findings observed immunohistochemically. There is also increased accumulation/redistribution of channel protein in the nerve most apparent proximal to the first constriction site. Intrathecal infusion of NT-3 significantly attenuates neuronal expression of Na v 1.8 and Na v 1.9 mRNA contralateral and most notably, ipsilateral to CCI, with a similar impact on relative protein expression at the level of the neuron and constricted nerve. We also observe reduced expression of the common neurotrophin receptor p75 in response to CCI that is not reversed by NT-3 in small to medium sized neurons and may confer an enhanced ability of NT-3 to signal via trkA, as has been previously shown in other cell types. These findings are consistent with an analgesic role for NT-3.

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“…These include such treatments as topical creams (for example, lidocaine), anticonvulsants, and tricyclic antidepressants (reviewed in Rogers et al, 2006).…”

Section: Potential Mechanisms Of Modulation Of Sodium Channel Expressmentioning

confidence: 99%

Neurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states

Wilson-Gerwing

Stucky

McComb

et al. 2008

Experimental Neurology

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“…Mutations in Nav 1.7 sodium channels can reduce the excitability of the sympathetic nervous system and cause hyperexcitability in small-caliber fibers. This would explain the edema, erythema, and pain of erythromelalgia 11 .…”

Section: Pain Mediated By the Sympathetic Nervous Systemmentioning

confidence: 98%

“…Mutações em canais de só-dio tipo Nav 1.7 podem provocar redução da excitabilidade do sistema nervoso simpático e hiperexcitabilidade de fibras de pequeno calibre. Isso explicaria o quadro de edema, vermelhidão e dor da eritromelalgia 11 .…”

Section: Canais De Sódiounclassified

“…Apesar da lesão periférica da fibra nervosa tipo C provocar redução no corno dorsal da medula espinal de SP, de neurotrofinas (BDNF), de receptores (VR1 e P2X 3 ), de canais de cálcio tipo N de alta voltagem, há regulação ascendente de canais TTX sensíveis (TTXs) tipo III e há translocação do corpo celular para o neuroma de canais de sódio TTX resistentes (TTXr), facilitando o aumento da excitabilidade nervosa 66 . Os canais TTXs tipo Nav 1.3, que têm característica cinética de fácil ativação e inativação, podem aumentar sua expressão em torno de duas a 30 vezes em modelos de axotomia do gânglio da raiz dorsal, da ligadura do nervo espinhal, da lesão constritiva crônica, da lesão difusa do nervo, da neuropatia diabética e da pós-herpética 11 .…”

Section: Dor Neuropática E Degeneração Do Nervounclassified

“…Although peripheral lesions of C fibers lead to a reduction of SP, neurotrophins (BDNF), receptors (VR1 and P2X 3 ), and type N high-voltage calcium channels in the dorsal horn of the spinal cord, there is ascending regulation of type III TTXsensitive (TTXs) channels and translocation of TTX-resistant (TTXr) sodium channels from the soma to the neuroma, increasing nerve excitability 66 . The expression of Nav 1.3 TTXs channels, whose kinetic characteristic is to be easily activated and inactivated, can increase by two to 30-fold in models of dorsal root ganglion axotomy, ligature of the spinal nerve, chronic constrictive damage, diffuse nerve damage, diabetic neuropathy, and post-herpetic neuropathy 11 .…”

Section: Neuropathic Pain and Nerve Degenerationmentioning

confidence: 99%

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Dor neuropática: aspectos neuroquímicos

Kraychete¹,

Gozzani²,

Kraychete³

2008

Rev. Bras. Anestesiol.

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Rev Bras AnestesiolARTIGO DE REVISÃO 2008; 58: 5: 492-505 REVIEW ARTICLE RESUMO Kraychete DC, Gozzani JL, Kraychete AC -Dor Neuropática -Aspectos Neuroquímicos. JUSTIFICATIVA E OBJETIVOS:A dor neuropática é causada por lesão ou inflamação do sistema nervoso. É síndrome complexa, com mecanismos biológicos pouco esclarecidos, envolvendo teorias inflamatórias e imunes. O objetivo desta revisão foi descrever os principais fatores biológicos relacionados com a dor neuropática, associando de forma lógica as hipóteses sugeridas pela literatura. CONTEÚDO:Foram descritos os principais neuromediadores, canais iônicos e células, incluindo as do sistema imune envolvidos na excitabilidade neuronal, assim como enfatizada possível seqüência de ativação ou interação desses agentes na alteração neuroplástica decorrente da agressão ao nervo.CONCLUSÕES: Do estudo, foi possível concluir que os avanços no conhecimento da fisiopatologia da dor neuropática podem determinar novos alvos para abordagem farmacológica dessa síndrome.Unitermos: DOR: neuropática; FISIOLOGIA: neurotransmissores. SUMMARYKraychete DC, Gozzani JL, Kraychete AC -Neuropathic PainNeurochemical Aspects. BACKGROUND AND OBJECTIVES:Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its biological mechanisms, involving inflammatory and immunologic theories, are not clear. The objective of this review was to describe the main biologic factors associated with neuropathic pain, making a logical association between hypotheses suggested in the literature. CONTENTS:The main neuromediators, ion channels, and cells, including cells in the nervous system involved in neuronal excitation are described, and the possible activation sequence or interaction among those agents in the neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS:It was possible to conclude that the advances on the knowledge of the pathophysiology of neuropathic pain can determine new pharmacologic approaches for this syndrome.

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