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Molecular Pain

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Open Access 01-12-2009 | Research

Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors

Authors: Patrick C Kerstein, Donato del Camino, Magdalene M Moran, Cheryl L Stucky

Published in: Molecular Pain | Issue 1/2009

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 Aδ 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.

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Title: Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors
Authors: Patrick C Kerstein
Donato del Camino
Magdalene M Moran
Cheryl L Stucky
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-5-19

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors

Abstract

Background

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusion

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