Sodium channelopathies and pain
Sodium channelopathies and pain
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DOI：
10.1007/s00424-009-0779-3
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发表时间：
2010-07-01
影响因子：
4.5
通讯作者：
Leffler, Andreas
中科院分区：
文献类型：
--
作者：
Lampert, Angelika;O'Reilly, Andrias O.;Leffler, Andreas
慢性疼痛通常代表一种严重的、使人衰弱的状况。全世界有高达10%的人口受到影响，许多患者对目前的治疗策略反应不佳。痛觉感受器探测到有害的情况，产生痛觉，并通过动作电位将信号传递给中枢神经系统。动作电位的快速上升是由电压门控钠通道介导的，其中已鉴定出9个成孔α亚基（Nav1.1-1.9）。不同的功能特性和不同的表达模式表明了每个亚基的特殊功能。Nav1.7和Nav1.8亚基已经成为参与外周疼痛处理和与炎症和组织损伤相关的疼痛敏感性增加的关键分子。编码Nav1.7的SCN9A基因的几个突变已被确定为不同遗传性疼痛综合征的重要细胞底物。这篇综述旨在涵盖我们对突变体Nav1.7的生物物理特性如何转化为伤害感受器异常电生的理解的最新进展。我们还概述了Nav1.8在外周疼痛处理和其他钠通道病变中的作用，这些钠通道病变与疼痛相关的疾病是一个重要组成部分。
Chronic pain often represents a severe, debilitating condition. Up to 10% of the worldwide population are affected, and many patients are poorly responsive to current treatment strategies. Nociceptors detect noxious conditions to produce the sensation of pain, and this signal is conveyed to the CNS by means of action potentials. The fast upstroke of action potentials is mediated by voltage-gated sodium channels, of which nine pore-forming alpha-subunits (Nav1.1-1.9) have been identified. Heterogeneous functional properties and distinct expression patterns denote specialized functions of each subunit. The Nav1.7 and Nav1.8 subunits have emerged as key molecules involved in peripheral pain processing and in the development of an increased pain sensitivity associated with inflammation and tissue injury. Several mutations in the SCN9A gene encoding for Nav1.7 have been identified as important cellular substrates for different heritable pain syndromes. This review aims to cover recent progress on our understanding of how biophysical properties of mutant Nav1.7 translate into an aberrant electrogenesis of nociceptors. We also recapitulate the role of Nav1.8 for peripheral pain processing and of additional sodium channelopathies which have been linked to disorders with pain as a significant component.