Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors
<p>Abstract</p> <p>Background</p> <p>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 req...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2009-04-01
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| Series: | Molecular Pain |
| Online Access: | http://www.molecularpain.com/content/5/1/19 |
| _version_ | 1818276428621283328 |
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| author | Moran Magdalene M del Camino Donato Kerstein Patrick C Stucky Cheryl L |
| author_facet | Moran Magdalene M del Camino Donato Kerstein Patrick C Stucky Cheryl L |
| author_sort | Moran Magdalene M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>ex-vivo </it>skin-nerve preparation to directly determine the contribution of TRPA1 to mechanical- and chemical-evoked responses at the level of the primary afferent terminal.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-12T22:45:30Z |
| format | Article |
| id | doaj.art-71ca0f0037a44e9da9da24def102a559 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-12-12T22:45:30Z |
| publishDate | 2009-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-71ca0f0037a44e9da9da24def102a5592022-12-22T00:09:13ZengSAGE PublishingMolecular Pain1744-80692009-04-01511910.1186/1744-8069-5-19Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptorsMoran Magdalene Mdel Camino DonatoKerstein Patrick CStucky Cheryl L<p>Abstract</p> <p>Background</p> <p>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 <it>ex-vivo </it>skin-nerve preparation to directly determine the contribution of TRPA1 to mechanical- and chemical-evoked responses at the level of the primary afferent terminal.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.molecularpain.com/content/5/1/19 |
| spellingShingle | Moran Magdalene M del Camino Donato Kerstein Patrick C Stucky Cheryl L Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors Molecular Pain |
| title | Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors |
| title_full | Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors |
| title_fullStr | Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors |
| title_full_unstemmed | Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors |
| title_short | Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors |
| title_sort | pharmacological blockade of trpa1 inhibits mechanical firing in nociceptors |
| url | http://www.molecularpain.com/content/5/1/19 |
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