Received for publication June 16, 2008.
Revised August 6, 2008.
Accepted for publication August 7, 2008.

General Anesthetics Sensitize the Capsaicin Receptor TRPV1

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. Recently, we found that pungent GAs excite sensory neurons by directly activating the TRPA1 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. Further, isoflurane directly activates TRPV1 following stimulation of protein kinase C. Similarly, 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 post-surgical pain and inflammation.

Key words: Capsaicin/vanilloid, Ion channel regulation, Gases/general anesthetics

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				N. Harrison and C. Nau Sensitization of Nociceptive Ion Channels by Inhaled Anesthetics--A Pain in the Gas? Mol. Pharmacol., November 1, 2008; 74(5): 1180 - 1182. [Abstract] [Full Text] [PDF]