Department of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg, Universitätsstrasse 17, 91054, Erlangen, Germany.
Pflugers Arch. 2010 Jul;460(2):249-63. doi: 10.1007/s00424-009-0779-3. Epub 2010 Jan 26.
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.
慢性疼痛常代表一种严重且使人虚弱的病症。全球多达 10%的人口受其影响，且许多患者对现有治疗策略的反应不佳。伤害感受器可检测有害状况以产生疼痛感觉，该信号通过动作电位传递至中枢神经系统。动作电位的快速上升由电压门控钠离子通道介导，其中已鉴定出九个形成孔的α亚基（Nav1.1-1.9）。各亚基具有不均一的功能特性和独特的表达模式，这表明它们具有特定的功能。Nav1.7 和 Nav1.8 亚基已成为涉及外周疼痛处理以及与炎症和组织损伤相关的疼痛敏感性增加的关键分子。已鉴定出编码 Nav1.7 的 SCN9A 基因中的多个突变是不同遗传性疼痛综合征的重要细胞底物。本综述旨在涵盖我们对突变型 Nav1.7 的生物物理特性如何转化为伤害感受器异常电生成的理解方面的最新进展。我们还概括了 Nav1.8 在周围疼痛处理中的作用以及与疼痛作为主要成分的疾病相关的其他钠通道病。
