The Open Pain Journal

2013, 6 : 154-164
Published online 2013 March 08. DOI: 10.2174/1876386301306010154
Publisher ID: TOPAINJ-6-154

RESEARCH ARTICLE
 Targeting TRPM8 for Pain Relief

Carlos Fernández-Peña and Felix Viana, *
Instituto de Neurociencias de Alicante, Universidad Miguel Hernandez-CSIC, Apartado 18, San Juan de Alicante, 03550 Spain.

* Address correspondence to this author at the Instituto de Neurociencias de Alicante, Universidad Miguel Hernandez-CSIC, Apartado 18, San Juan de Alicante, 03550 Spain; Tel: 34-96-591-9347; Fax: 34-96-591-9561; E-mail: felix.viana@umh.es

ABSTRACT

Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in peripheral cold thermoreceptors and plays a fundamental role in sensing mild, cool temperatures. In addition, cumulative evidence obtained in humans and different animals models, combined with pharmacological and gene silencing techniques, suggest that TRPM8 may also play a role in cold discomfort and the pathophysiology of cold pain. This article reviews the available evidence in a critical fashion. In addition, the article reviews the possible role of TRPM8 in basal tearing, cold urticaria and airway irritation. Collectively, these results suggest that pharmacological modulators of TRPM8 could have potential indications in a variety of conditions, including dry eye disease, airway irritation, teeth hypersensitivity, migraine and neuropathic pain. However, additional studies, especially in humans, are needed to verify these preliminary observations. The paucity of potent, specific pharmacological TRPM8 antagonists available is a current limitation for further progress in this field.

Keywords:

Cold, Thermoreceptor, Menthol, Icilin, Somatosensory Transduction, TRPA1, TRP Channel.