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

287 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

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Hyperalgesia
Nociception
Pharmacology
Transient Receptor Potential Channels
Masks
Ion Channels
Knockout Mice
Pain
Inhibition (Psychology)

ASJC Scopus subject areas

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

Cite this

Petrus, M., Peier, A. M., Bandell, M., Hwang, S. W., Huynh, T., Olney, N., ... 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

A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. / Petrus, Matt; Peier, Andrea M.; Bandell, Michael; Hwang, Sun Wook; Huynh, Truc; Olney, Nicholas; Jegla, Tim; Patapoutian, Ardem.

In: Molecular Pain, Vol. 3, 40, 17.12.2007.

Research output: Contribution to journalArticle

Petrus, M, Peier, AM, Bandell, M, Hwang, SW, Huynh, T, Olney, N, Jegla, T & Patapoutian, A 2007, 'A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition', Molecular Pain, vol. 3, 40. https://doi.org/10.1186/1744-8069-3-40
Petrus, Matt ; Peier, Andrea M. ; Bandell, Michael ; Hwang, Sun Wook ; Huynh, Truc ; Olney, Nicholas ; Jegla, Tim ; Patapoutian, Ardem. / A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. In: Molecular Pain. 2007 ; Vol. 3.
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