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

Matt Petrus, Andrea M. Peier, Michael Bandell, Sun Wook Hwang, Truc Huynh, Nicholas Olney, Tim Jegla, Ardem Patapoutian

Research output: Contribution to journalArticle

299 Citations (Scopus)

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.

Original languageEnglish
Article number40
JournalMolecular pain
Volume3
DOIs
Publication statusPublished - 2007 Dec 17

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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    Petrus, M., Peier, A. M., Bandell, M., Hwang, S. W., Huynh, T., Olney, N., Jegla, T., & Patapoutian, A. (2007). A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Molecular pain, 3, [40]. https://doi.org/10.1186/1744-8069-3-40