RESEARCH ARTICLE


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



Olivier Radresaa, Henrik Dahllöfb, Eva Nymanb, Andreas Noltingb, Jeffrey S. Alberta, Patrick Raboisson*, b
a AstraZeneca R&D Montreal, St-Laurent, H4S 1Z9, Canada
b AstraZeneca R&D Södertälje, Södertälje SE-151 85,Sweden


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Creative Commons License
© 2013 Radresa et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* 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.

Keywords: TRPA1, TRP, AITC, Cinnamaldehyde, Drug Discovery, Analgesic, Pain, Asthma, COPD.