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Science 288 (5464): 306-313

Copyright © 2000 by the American Association for the Advancement of Science

Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor

M. J. Caterina, 1* A. Leffler, 3 A. B. Malmberg, 2dagger W. J. Martin, 2ddagger J. Trafton, 2 K. R. Petersen-Zeitz, 2 M. Koltzenburg, 3 A. I. Basbaum, 2 D. Julius 1§

The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43°C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.

1 Department of Cellular and Molecular Pharmacology,
2 Departments of Anatomy and Physiology and the W. M. Keck Center for Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0450, USA.
3 Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
*   Present address: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

dagger    Present address: Neurobiology Unit, Roche Bioscience, Palo Alto, CA 94304-1397, USA.

ddagger    Present address: Merck Research Laboratories, Rahway, NJ 07065, USA.

§   To whom correspondence should be addressed. E-mail: julius{at}socrates.ucsf.edu

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   Abstract »    Full Text »    PDF »
Distinct Modulations of Human Capsaicin Receptor by Protons and Magnesium through Different Domains.
S. Wang, K. Poon, R. E. Oswald, and H. h. Chuang (2010)
J. Biol. Chem. 285, 11547-11556
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Trichostatin A, a histone deacetylase inhibitor, reduces lesion growth and hyperalgesia in experimentally induced endometriosis in mice.
Y. Lu, J. Nie, X. Liu, Y. Zheng, and S.-W. Guo (2010)
Hum. Reprod. 25, 1014-1025
   Abstract »    Full Text »    PDF »
Physiological Basis of Tingling Paresthesia Evokedby Hydroxy-{alpha}-Sanshool.
R. C. Lennertz, M. Tsunozaki, D. M. Bautista, and C. L. Stucky (2010)
J. Neurosci. 30, 4353-4361
   Abstract »    Full Text »    PDF »
Ecto-5'-Nucleotidase (CD73) Inhibits Nociception by Hydrolyzing AMP to Adenosine in Nociceptive Circuits.
N. A. Sowa, B. Taylor-Blake, and M. J. Zylka (2010)
J. Neurosci. 30, 2235-2244
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Pharmacologic Antagonism of the Oral Aversive Taste-Directed Response to Capsaicin in a Mouse Brief Access Taste Aversion Assay.
D. J. Long, H. R. Devantier, F. X. Brennan, R. W. Bryant, F. R. Salemme, and R. K. Palmer (2010)
J. Pharmacol. Exp. Ther. 332, 525-530
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TRPV1 Gene Deficiency Attenuates Miniature EPSC Potentiation Induced by Mannitol and Angiotensin II in Supraoptic Magnocellular Neurons.
T. Yokoyama, T. Saito, T. Ohbuchi, H. Hashimoto, H. Suzuki, H. Otsubo, H. Fujihara, T. Nagatomo, and Y. Ueta (2010)
J. Neurosci. 30, 876-884
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TRP channels: new targets for visceral pain.
L A Blackshaw, S M Brierley, and P A Hughes (2010)
Gut 59, 126-135
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17{beta}-Estradiol Mediates the Sex Difference in Capsaicin-Induced Nociception in Rats.
Y.-C. Lu, C.-W. Chen, S.-Y. Wang, and F.-S. Wu (2009)
J. Pharmacol. Exp. Ther. 331, 1104-1110
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Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension.
Y. Wang and D. H. Wang (2009)
Am J Physiol Renal Physiol 297, F1550-F1559
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Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification.
H.-h. Chuang and S. Lin (2009)
PNAS 106, 20097-20102
   Abstract »    Full Text »    PDF »
Fat location defines sensation.
U. Oh and J. N. Wood (2009)
PNAS 106, 18435-18436
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Differential contribution of SNARE-dependent exocytosis to inflammatory potentiation of TRPV1 in nociceptors.
M. Camprubi-Robles, R. Planells-Cases, and A. Ferrer-Montiel (2009)
FASEB J 23, 3722-3733
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Thermosensory and mechanosensory perception in human genetic disease.
P. L. Tan and N. Katsanis (2009)
Hum. Mol. Genet. 18, R146-R155
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Inhibitor {kappa}B Kinase {beta} Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity.
V. Bockhart, C. E. Constantin, A. Haussler, N. Wijnvoord, M. Kanngiesser, T. Myrczek, G. Pickert, L. Popp, J.-M. Sobotzik, M. Pasparakis, et al. (2009)
J. Neurosci. 29, 12919-12929
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