General anesthetics sensitize the capsaicin receptor transient receptor potential V1.
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.
Cornett
Paul M
PM
Department of Pharmacology, Georgetown University, 3900 Reservoir Rd., NW, Washington DC 20007, USA.
Matta
José A
JA
Ahern
Gerard P
GP
D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006801:Humans; D051379:Mice; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects*; D014982:Xenopus laevis
D018681:Anesthetics, General; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D011493:Protein Kinase C; D002211:Capsaicin; D001920:Bradykinin