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.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Bradykinin / adverse effects
  • CHO Cells
  • Calcium Signaling / drug effects
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Humans
  • Hyperalgesia / genetics
  • Hyperalgesia / metabolism*
  • Hyperalgesia / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oocytes
  • Pain Measurement / methods
  • Rats
  • Rats, Sprague-Dawley
  • TRPA1 Cation Channel
  • Transfection / methods
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / deficiency
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / physiology*
  • Xenopus


  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Bradykinin