Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 105 (25): 8784-8789

Copyright © 2008 by the National Academy of Sciences.

From the Cover


BIOLOGICAL SCIENCES / PHARMACOLOGY

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

José A. Matta*, Paul M. Cornett*, Rosa L. Miyares*, Ken Abe{dagger}, Niaz Sahibzada*, and Gerard P. Ahern*,{ddagger}

Departments of *Pharmacology and {dagger}Physiology and Biophysics, Georgetown University, 3900 Reservoir Road, NW, Washington, DC 20007

Edited by Ramón Latorre, Centro de Neurociencias, Universidad de Valparaíso, Valparaíso, and approved April 21, 2008

Received for publication November 21, 2007.

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.

Key Words: TRPA1 • TRPV1 • isothiocyanate • mustard oil • isoflurane


Author contributions: J.A.M., P.M.C., and G.P.A. designed research; J.A.M., P.M.C., R.L.M., K.A., N.S., and G.P.A. performed research; J.A.M., P.M.C., R.L.M., N.S., and G.P.A. analyzed data; and J.A.M., R.L.M., and G.P.A. wrote the paper.

Conflict of interest: Georgetown University has filed a provisional patent relating to this study.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0711038105/DCSupplemental.

{ddagger}To whom correspondence should be addressed. E-mail: gpa3{at}georgetown.edu

© 2008 by The National Academy of Sciences of the USA


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease.
M. S. Steinhoff, B. von Mentzer, P. Geppetti, C. Pothoulakis, and N. W. Bunnett (2014)
Physiol Rev 94, 265-301
   Abstract »    Full Text »    PDF »
Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia.
F. Vanden Abeele, A. Kondratskyi, C. Dubois, G. Shapovalov, D. Gkika, J. Busserolles, Y. Shuba, R. Skryma, and N. Prevarskaya (2013)
J. Cell Sci. 126, 4479-4489
   Abstract »    Full Text »    PDF »
Mechanisms of Transient Receptor Potential Vanilloid 1 Activation and Sensitization by Allyl Isothiocyanate.
M. Gees, Y. A. Alpizar, B. Boonen, A. Sanchez, W. Everaerts, A. Segal, F. Xue, A. Janssens, G. Owsianik, B. Nilius, et al. (2013)
Mol. Pharmacol. 84, 325-334
   Abstract »    Full Text »    PDF »
The Ion Channel TRPA1 Is Required for Chronic Itch.
S. R. Wilson, A. M. Nelson, L. Batia, T. Morita, D. Estandian, D. M. Owens, E. A. Lumpkin, and D. M. Bautista (2013)
J. Neurosci. 33, 9283-9294
   Abstract »    Full Text »    PDF »
Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin.
N. Hatano, H. Suzuki, Y. Muraki, and K. Muraki (2013)
Am J Physiol Cell Physiol 304, C354-C361
   Abstract »    Full Text »    PDF »
Activation of Spinal {micro}- and {delta}-Opioid Receptors Potently Inhibits Substance P Release Induced by Peripheral Noxious Stimuli.
H. Beaudry, D. Dubois, and L. Gendron (2011)
J. Neurosci. 31, 13068-13077
   Abstract »    Full Text »    PDF »
Irritating channels: the case of TRPA1.
B. Nilius, J. Prenen, and G. Owsianik (2011)
J. Physiol. 589, 1543-1549
   Abstract »    Full Text »    PDF »
When does acute pain become chronic?.
C. Voscopoulos and M. Lema (2010)
Br. J. Anaesth. 105, i69-i85
   Abstract »    Full Text »    PDF »
The General Anesthetic Propofol Excites Nociceptors by Activating TRPV1 and TRPA1 Rather than GABAA Receptors.
M. J. M. Fischer, A. Leffler, F. Niedermirtl, K. Kistner, M. Eberhardt, P. W. Reeh, and C. Nau (2010)
J. Biol. Chem. 285, 34781-34792
   Abstract »    Full Text »    PDF »
Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice.
E. Ceppa, F. Cattaruzza, V. Lyo, S. Amadesi, J.-C. Pelayo, D. P. Poole, N. Vaksman, W. Liedtke, D. M. Cohen, E. F. Grady, et al. (2010)
Am J Physiol Gastrointest Liver Physiol 299, G556-G571
   Abstract »    Full Text »    PDF »
Desflurane but not sevoflurane can increase lung resistance via tachykinin pathways.
J.-I. Satoh, M. Yamakage, T. Kobayashi, N. Tohse, H. Watanabe, and A. Namiki (2009)
Br. J. Anaesth. 102, 704-713
   Abstract »    Full Text »    PDF »
Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control.
B. F. Bessac and S.-E. Jordt (2008)
Physiology 23, 360-370
   Abstract »    Full Text »    PDF »
A Double TRPtych: Six Views of Transient Receptor Potential Channels in Disease and Health.
R. A. Cornell, M. Aarts, D. Bautista, J. Garcia-Anoveros, K. Kiselyov, and E. R. Liman (2008)
J. Neurosci. 28, 11778-11784
   Abstract »    Full Text »    PDF »
Sensitization of Nociceptive Ion Channels by Inhaled Anesthetics--A Pain in the Gas?.
N. Harrison and C. Nau (2008)
Mol. Pharmacol. 74, 1180-1182
   Abstract »    Full Text »    PDF »
General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1.
P. M. Cornett, J. A. Matta, and G. P. Ahern (2008)
Mol. Pharmacol. 74, 1261-1268
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 05 August 2008.
N. R. Gough and A. M. VanHook (2008)
Science Signaling 1, pc7
   Abstract »    Full Text »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882