acid-sensing ion channels and pain酸感性离子通道和痛苦.pdfVIP

Pharmaceuticals 2010, 3, 1411-1425; doi:10.3390/ph3051411 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Acid-Sensing Ion Channels and Pain Qihai Gu * and Lu-Yuan Lee Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA; E-Mails: lylee@ (L.Y.L.) * Author to whom correspondence should be addressed; E-Mail: qgu2@ Tel.: +1-859-323-5348; Fax: +1-859-323-1070. Received: 02 April 2010; in revised form: 14 April 2010 / Accepted: 07 May 2010 / Published: 11 May 2010 Abstract: Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management. Keywords: acid sensing ion channel; acidosis; inflammation; nociceptor; pain 1. Introduction Tissue acidosis occurs in various physiological and pathophysiological states, including inflammation, infection, ischemia, cancer, tissue injury and metabolic stress [14]. It has long been known that extracellular acidosis elicits pain [1,5]. The local drop in pH is first detected by primary sen