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PMID: 18574153 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 25 ·2008-06-24 ·Pages 8784-9

Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP

Abstract

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.

MeSH Terms
Anesthetics, General/pharmacology Animals Ankyrins Calcium Channels/metabolism Humans Inflammation/metabolism,physiopathology Isoflurane/pharmacology Mice Pain/metabolism,physiopathology Rats TRPA1 Cation Channel TRPC Cation Channels TRPM Cation Channels/metabolism TRPV Cation Channels/metabolism Transient Receptor Potential Channels/metabolism
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Matta José A
Departments of Pharmacology and Physiology and Biophysics, Georgetown University, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
Cornett Paul M
Miyares Rosa L
Abe Ken
Sahibzada Niaz
Ahern Gerard P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0711038105
Published
2008-06-24
Epub
2008-00-23
Pages
8784-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2438393
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0711038105 PMC Full Text View journal details
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