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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}

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Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.
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J. Biol. Chem. 286, 9688-9698
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Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses.
K. Ono, M. Tsukamoto-Yasui, Y. Hara-Kimura, N. Inoue, Y. Nogusa, Y. Okabe, K. Nagashima, and F. Kato (2011)
J Appl Physiol 110, 789-798
   Abstract »    Full Text »    PDF »
A spicy family tree: TRPV1 and its thermoceptive and nociceptive lineage.
D. D. McKemy (2011)
EMBO J. 30, 453-455
   Abstract »    Full Text »    PDF »
TRPV1-lineage neurons are required for thermal sensation.
S. K. Mishra, S. M. Tisel, P. Orestes, S. K. Bhangoo, and M. A. Hoon (2011)
EMBO J. 30, 582-593
   Abstract »    Full Text »    PDF »
Thermoregulatory Phenotype of the Trpv1 Knockout Mouse: Thermoeffector Dysbalance with Hyperkinesis.
A. Garami, E. Pakai, D. L. Oliveira, A. A. Steiner, S. P. Wanner, M. C. Almeida, V. A. Lesnikov, N. R. Gavva, and A. A. Romanovsky (2011)
J. Neurosci. 31, 1721-1733
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2.
R. G. Pertwee, A. C. Howlett, M. E. Abood, S. P. H. Alexander, V. Di Marzo, M. R. Elphick, P. J. Greasley, H. S. Hansen, G. Kunos, K. Mackie, et al. (2010)
Pharmacol. Rev. 62, 588-631
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TRPA1 Contributes to Cold Hypersensitivity.
D. del Camino, S. Murphy, M. Heiry, L. B. Barrett, T. J. Earley, C. A. Cook, M. J. Petrus, M. Zhao, M. D'Amours, N. Deering, et al. (2010)
J. Neurosci. 30, 15165-15174
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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
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Chronic Spontaneous Activity Generated in the Somata of Primary Nociceptors Is Associated with Pain-Related Behavior after Spinal Cord Injury.
S. S. Bedi, Q. Yang, R. J. Crook, J. Du, Z. Wu, H. M. Fishman, R. J. Grill, S. M. Carlton, and E. T. Walters (2010)
J. Neurosci. 30, 14870-14882
   Abstract »    Full Text »    PDF »
Modulation of single-channel properties of TRPV1 by phosphorylation.
M. Studer and P. A. McNaughton (2010)
J. Physiol. 588, 3743-3756
   Abstract »    Full Text »    PDF »
Mas-related G-protein-coupled receptors inhibit pathological pain in mice.
Y. Guan, Q. Liu, Z. Tang, S. N. Raja, D. J. Anderson, and X. Dong (2010)
PNAS 107, 15933-15938
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family.
L.-J. Wu, T.-B. Sweet, and D. E. Clapham (2010)
Pharmacol. Rev. 62, 381-404
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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 »
Cocarcinogenic Effect of Capsaicin Involves Activation of EGFR Signaling but Not TRPV1.
M. K. Hwang, A. M. Bode, S. Byun, N. R. Song, H. J. Lee, K. W. Lee, and Z. Dong (2010)
Cancer Res. 70, 6859-6869
   Abstract »    Full Text »    PDF »

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