Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
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 degrees 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.
Caterina
M J
MJ
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143-0450, USA.
Leffler
A
A
Malmberg
A B
AB
Martin
W J
WJ
Trafton
J
J
Petersen-Zeitz
K R
KR
Koltzenburg
M
M
Basbaum
A I
AI
Julius
D
D
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D018390:Gene Targeting; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold; D011955:Receptors, Drug / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D050916:TRPV Cation Channels
D004224:Diterpenes; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C024353:resiniferatoxin; D002211:Capsaicin; D002118:Calcium