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Molecular Pharmacology

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Research ArticleArticle

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Paul M. Cornett, José A. Matta and Gerard P. Ahern
Molecular Pharmacology November 2008, 74 (5) 1261-1268; DOI: https://doi.org/10.1124/mol.108.049684
Paul M. Cornett
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José A. Matta
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Gerard P. Ahern
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Abstract

General anesthetics (GAs) are central nervous system depressants that render patients unresponsive to external stimuli. In contrast, many of these agents are also known to stimulate peripheral sensory nerves, raising the possibility that they may exacerbate tissue inflammation. We have found that pungent GAs excite sensory neurons by directly activating the transient receptor potential (TRP) A1 ion channel. Here, we show that GAs also sensitize the capsaicin receptor TRPV1, a key ion channel expressed in nociceptive neurons. Clinically relevant concentrations of isoflurane, sevoflurane, enflurane, and desflurane sensitize TRPV1 to capsaicin and protons and reduce the threshold for heat activation. Furthermore, isoflurane directly activates TRPV1 after stimulation of protein kinase C. Likewise, isoflurane excites TRPV1 and sensory neurons during concomitant application of bradykinin, a key inflammatory mediator formed during tissue injury. Thus, GAs can enhance the activation of TRPV1 that occurs during surgically induced tissue damage. These results support the hypothesis that some GAs, through direct actions at TRP channels, increase postsurgical pain and inflammation.

Footnotes

  • This study was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, and the United States Navy.

  • ABBREVIATIONS: VGA, volatile general anesthetic; GA, general anesthetic; TRP, transient receptor potential; CNS, central nervous system; MAC, minimum alveolar concentration; HEK, human embryonic kidney; PKC, protein kinase C; BK, bradykinin; MES, 4-morpholineethanesulfonic acid; AMG9810, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide; capsaicin, N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-eneamide; capsazepine, N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2-H-2-benzazepine-2-carbothioamide; PDBu, phorbol 12, 13-dibutyrate.

    • Received June 13, 2008.
    • Accepted August 7, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 74 (5)
Molecular Pharmacology
Vol. 74, Issue 5
1 Nov 2008
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Research ArticleArticle

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Paul M. Cornett, José A. Matta and Gerard P. Ahern
Molecular Pharmacology November 1, 2008, 74 (5) 1261-1268; DOI: https://doi.org/10.1124/mol.108.049684

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Research ArticleArticle

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Paul M. Cornett, José A. Matta and Gerard P. Ahern
Molecular Pharmacology November 1, 2008, 74 (5) 1261-1268; DOI: https://doi.org/10.1124/mol.108.049684
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