General anesthetics activate a nociceptive ion channel to enhance pain and inflammation

Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8784-9. doi: 10.1073/pnas.0711038105. Epub 2008 Jun 23.


General anesthetics (GAs) have transformed surgery through their actions to depress the central nervous system and blunt the perception of surgical insults. Counterintuitively, many of these agents activate peripheral nociceptive neurons. However, the underlying mechanisms and significance of these effects have not been explored. Here, we show that clinical concentrations of noxious i.v. and inhalation GAs excite sensory neurons by selectively activating TRPA1, a key ion channel in the pain pathway. Further, these GAs induce pain-related responses in mice that are abolished in TRPA1-null animals. Significantly, TRPA1-dependent neurogenic inflammation is greater in mice anesthetized with pungent compared with nonpungent anesthetics. Thus, our results show that TRPA1 is essential for sensing noxious GAs. The pronociceptive effects of GAs combined with surgical tissue damage could lead to a paradoxical increase in postoperative pain and inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, General / pharmacology*
  • Animals
  • Ankyrins
  • Calcium Channels / metabolism*
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Isoflurane / pharmacology*
  • Mice
  • Pain / metabolism
  • Pain / physiopathology*
  • Rats
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPM Cation Channels / metabolism
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / metabolism*


  • Anesthetics, General
  • Ankyrins
  • Calcium Channels
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPM Cation Channels
  • TRPV Cation Channels
  • Transient Receptor Potential Channels
  • Trpa1 protein, rat
  • Trpm8 protein, rat
  • Trpv1 protein, rat
  • Isoflurane