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PMID: 18086313 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular pain ·Vol. 3 ·2007-12-17 ·Pages 40

Petrus M, Peier AM, Bandell M, Hwang SW, Huynh T, Olney N, Jegla T, Patapoutian A

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.

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,metabolism,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,deficiency,genetics,physiology Xenopus
Chemicals
TRPA1 Cation Channel Transient Receptor Potential Channels Trpa1 protein, mouse Bradykinin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Petrus Matt
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA. [email protected]
Peier Andrea M
Bandell Michael
Hwang Sun Wook
Huynh Truc
Olney Nicholas
Jegla Tim
Patapoutian Ardem
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Article Info
Journal
Molecular pain
Abbr.
Mol Pain
ISSN
1744-8069
DOI
10.1186/1744-8069-3-40
Email
[email protected]
Published
2007-12-17
Epub
2007-00-17
Pages
40
Language
English
Region
United States
NLM ID
101242662
PMCID
PMC2222610
Subset
IM
Grants
NIDCR NIH HHS · DE016927 · United States
NIDCR NIH HHS · R01 DE016927 · United States
NIA NIH HHS · T32 AG023481 · United States
NINDS NIH HHS · R01 NS046303 · United States
NINDS NIH HHS · NS046303 · United States
External Links
PubMed source DOI: 10.1186/1744-8069-3-40 PMC Full Text View journal details
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