TRPA1 Contributes to Cold Hypersensitivity

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 Nov 12

PMID 21068322

Citations 144

Authors

Donato Del Camino

Sarah Murphy

Melissa Heiry

Lee B Barrett

Taryn J Earley

Colby A Cook

Matt J Petrus

Michael Zhao

Marc DAmours

Nate Deering

Gary J Brenner

Michael Costigan

Neil J Hayward

Jayhong A Chong

Christopher M Fanger

Clifford J Woolf

Ardem Patapoutian

Magdalene M Moran

Affiliations

Soon will be listed here.

Abstract

TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

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