Roles of TRPA1 in Pain Pathophysiology and Implications for theDevelopment of a New Class of Analgesic Drugs

摘要

The Transient Receptor Potential A1 (TRPA1) ion channel has evolved in animals to respond to signals from avariety of sensory stimuli. Many structural determinants of its multimodal activation have been identified to date. TRPA1activities include responses to exogenous chemical irritants, responses to endogenous inflammatory mediators, zinc, voltage,temperature or stretch and subtle yet critical modulation by calcium ions. TRPA1 has emerged as an important targetfor several types of pain and inflammatory conditions because of its limited expression profile and its demonstrated rolesin mediating different types of pain and sensitization of peripheral sensory afferents. Despite observed species differencesin channel pharmacology, recent genetic evidence in human brings some hope that preclinical efficacy in disease modelswill translate to patient condition. During the past decade, various groups have investigated the development of a newclass of analgesic drugs or anti-tussive agents aimed at blocking TRPA1 activity in primary sensory afferents. Severalcompanies are advancing toward clinical proof of concept studies. This review aims to summarize key advances in theunderstanding of TRPA1 with regard to its roles and implications for patient conditions.