The Open Pain Journal
2013, 6 : 137-153Published online 2013 March 08. DOI: 10.2174/1876386301306010137
Publisher ID: TOPAINJ-6-137
RESEARCH ARTICLE
Roles of TRPA1 in Pain Pathophysiology and Implications for the Development of a New Class of Analgesic Drugs
b AstraZeneca R&D Södertälje, Södertälje SE-151 85,Sweden
* Address correspondence to this author at Galderma R&D, 2400 route des Colles - Les Templiers, 06410 Biot, France; Tel: +33(0)492954762; Fax: +33(0)493957071; E-mail: patrick.raboisson.1@gmail.com
ABSTRACT
The Transient Receptor Potential A1 (TRPA1) ion channel has evolved in animals to respond to signals from a variety of sensory stimuli. Many structural determinants of its multimodal activation have been identified to date. TRPA1 activities 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 target for several types of pain and inflammatory conditions because of its limited expression profile and its demonstrated roles in mediating different types of pain and sensitization of peripheral sensory afferents. Despite observed species differences in channel pharmacology, recent genetic evidence in human brings some hope that preclinical efficacy in disease models will translate to patient condition. During the past decade, various groups have investigated the development of a new class of analgesic drugs or anti-tussive agents aimed at blocking TRPA1 activity in primary sensory afferents. Several companies are advancing toward clinical proof of concept studies. This review aims to summarize key advances in the understanding of TRPA1 with regard to its roles and implications for patient conditions.