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Science 14 April 2000:
Vol. 288. no. 5464, pp. 306 - 313
DOI: 10.1126/science.288.5464.306
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Research Articles

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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Both Ca2+-permeable and -impermeable AMPA receptors contribute to primary synaptic drive onto rat dorsal horn neurons.
C.-K. Tong and A. B. MacDermott (2006)
J. Physiol. 575, 133-144
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Prolactin Modulates TRPV1 in Female Rat Trigeminal Sensory Neurons.
A. Diogenes, A. M. Patwardhan, N. A. Jeske, N. B. Ruparel, V. Goffin, A. N. Akopian, and K. M. Hargreaves (2006)
J. Neurosci. 26, 8126-8136
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The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin.
A. M. Patwardhan, N. A. Jeske, T. J. Price, N. Gamper, A. N. Akopian, and K. M. Hargreaves (2006)
PNAS 103, 11393-11398
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Characterization of acid signaling in rat vagal pulmonary sensory neuron