RT Journal Article SR Electronic T1 General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1 JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1261 OP 1268 DO 10.1124/mol.108.049684 VO 74 IS 5 A1 Paul M. Cornett A1 José A. Matta A1 Gerard P. Ahern YR 2008 UL http://molpharm.aspetjournals.org/content/74/5/1261.abstract AB 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. The American Society for Pharmacology and Experimental Therapeutics