Voltage-gated sodium channels and pain pathways
Voltage-gated sodium channels and pain pathways
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DOI：
10.1002/neu.20094
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Baker, MD
中科院分区：
文献类型：
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作者：
Wood, JN;Boorman, JP;Baker, MD
急性、炎性和神经性疼痛均可通过钠通道阻滞剂（如利多卡因）局部治疗减轻或消除。因此，驱动疼痛感知的外周输入依赖于功能性电压门控钠通道的存在。值得注意的是，两个电压门控钠通道基因（Na（V）1.8和Na（V）1.9）选择性地在损伤敏感外周神经元中表达，而第三个通道（Na（V）1.7）主要在感觉和交感神经元中发现。胚胎通道（Na（V）1.3）也在受损的外周神经中上调，并且与神经性疼痛状态中增加的电兴奋性相关。反义和敲除研究的组合支持这些钠通道在疼痛通路中的专门作用，芋螺毒素的药理学研究表明，同种型特异性拮抗剂应该是可行的。总之，这些数据表明，同种型特异性钠通道阻滞剂可能是有用的镇痛药。(C)2004 Wiley Periodicals，Inc.
Acute, inflammatory, and neuropathic pain can all be attenuated or abolished by local treatment with sodium channel blockers such as lidocaine. The peripheral input that drives pain perception thus depends on the presence of functional voltage-gated sodium channels. Remarkably, two voltage-gated sodium channel genes (Na(V)1.8 and Na(V)1.9) are expressed selectively in damage-sensing peripheral neurons, while a third channel (Na(V)1.7) is found predominantly in sensory and sympathetic neurons. An embryonic channel (Na(V)1.3) is also upregulated in damaged peripheral nerves and associated with increased electrical excitability in neuropathic pain states. A combination of antisense and knock-out studies support a specialized role for these sodium channels in pain pathways, and pharmacological studies with conotoxins suggest that isotype-specific antagonists should be feasible. Taken together, these data suggest that isotype-specific sodium channel blockers could be useful analgesics. (C) 2004 Wiley Periodicals, Inc.