Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Ann N Y Acad Sci. 2010 Jan;1184:196-207. doi: 10.1111/j.1749-6632.2009.05110.x.
The literature currently suggests that voltage-gated sodium channels play a major role in the pathogenesis of neuropathic pain. Alterations in the expression and targeting of specific sodium channels within injured dorsal root ganglia neurons appear to predispose the neurons to abnormal firing properties, allowing for the development of neuropathic pain. Mutations of one particular sodium channel (Na(v)1.7) have been shown to cause inherited neuropathic pain in humans, specifically in erythromelalgia and paroxysmal extreme pain disorder. Inherited erythromelalgia is the first human pain syndrome to be understood at a molecular level, having been linked to gain-of-function mutations of Na(v)1.7. Conversely, a loss-of-function of the Na(v)1.7 channel can produce channelopathy-associated insensitivity to pain. Therefore, the Na(v)1.7 channel may provide a unique target for the pharmacotherapy of pain in humans. In this review article we summarize current knowledge regarding several different disease manifestations arising from changes within the Na(v)1.7 channel.
目前的文献表明，电压门控钠离子通道在神经性疼痛的发病机制中起主要作用。受伤背根神经节神经元中特定钠离子通道的表达和靶向改变似乎使神经元容易产生异常放电特性，从而导致神经性疼痛的发生。特定钠离子通道（Nav1.7）的突变已被证明可导致人类遗传性神经性疼痛，特别是在红斑性肢痛症和阵发性剧痛症中。遗传性红斑性肢痛症是第一个在分子水平上被理解的人类疼痛综合征，与 Nav1.7 的功能获得性突变有关。相反，Nav1.7 通道的功能丧失会导致与通道病相关的对疼痛不敏感。因此，Nav1.7 通道可能为人类疼痛的药物治疗提供一个独特的靶点。在这篇综述文章中，我们总结了目前关于 Nav1.7 通道变化引起的几种不同疾病表现的知识。
