Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor
M. J. Caterina,
1*
A. Leffler,
3
A. B. Malmberg,
2
W. J. Martin,
2
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.
Present address: Neurobiology Unit, Roche Bioscience,
Palo Alto, CA 94304-1397, USA.
Present address: Merck Research Laboratories, Rahway,
NJ 07065, USA.
§
To whom correspondence should be addressed. E-mail:
julius{at}socrates.ucsf.edu
