1. Academic Validation
  2. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

  • Mol Pain. 2007 Dec 17;3:40. doi: 10.1186/1744-8069-3-40.
Matt Petrus 1 Andrea M Peier Michael Bandell Sun Wook Hwang Truc Huynh Nicholas Olney Tim Jegla Ardem Patapoutian
Affiliations

Affiliation

  • 1 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA. mpetrus@gnf.org
Abstract

Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18) that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

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