Faculty Collaboration Database

Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors. Mol Pain 2009 Apr 21;5:19

Date

04/23/2009

Pubmed ID

19383149

Pubmed Central ID

PMC2681449

DOI

10.1186/1744-8069-5-19

Scopus ID

2-s2.0-65649141656 (requires institutional sign-in at Scopus site)   133 Citations

Abstract

BACKGROUND: TRPA1 has been implicated in both chemo- and mechanosensation. Recent work demonstrates that inhibiting TRPA1 function reduces mechanical hypersensitivity produced by inflammation. Furthermore, a broad range of chemical irritants require functional TRPA1 to exert their effects. In this study we use the ex-vivo skin-nerve preparation to directly determine the contribution of TRPA1 to mechanical- and chemical-evoked responses at the level of the primary afferent terminal.

RESULTS: Acute application of HC-030031, a selective TRPA1 antagonist, inhibited all formalin responses in rat C fibers but had no effect on TRPV1 function, assessed by capsaicin responsiveness. Genetic ablation experiments corroborated the pharmacological findings as C fibers from wild type mice responded to both formalin and capsaicin, but fibers from their TRPA1-deficient littermates responded only to capsaicin. HC-030031 markedly reduced the mechanically-evoked action potential firing in rat and wild type mouse C fibers, particularly at high-intensity forces, but had no effect on the mechanical responsiveness of Adelta fiber nociceptors. Furthermore, HC-030031 had no effect on mechanically-evoked firing in C fibers from TRPA1-deficient mice, indicating that HC-030031 inhibits mechanically-evoked firing via a TRPA1-dependent mechanism.

CONCLUSION: Our data show that acute pharmacological blockade of TRPA1 at the cutaneous receptive field inhibits formalin-evoked activation and markedly reduces mechanically-evoked action potential firing in C fibers. Thus, functional TRPA1 at sensory afferent terminals in skin is required for their responsiveness to both noxious chemical and mechanical stimuli.

Author List

Kerstein PC, del Camino D, Moran MM, Stucky CL

Author

Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Capsaicin
Female
Formaldehyde
Male
Membrane Transport Modulators
Mice
Mice, Knockout
Nerve Fibers, Myelinated
Nerve Fibers, Unmyelinated
Nociceptors
Rats
Rats, Sprague-Dawley
TRPA1 Cation Channel
Transient Receptor Potential Channels