Impaired nociception and pain sensation in mice lacking the capsaicin receptor

The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by pri mary sensory neurons of the "pain" pathway. Heterologously expressed VR1 ca n be activated by vanilloid compounds, protons, or heat (>43 degrees C), bu t whether this channel contributes to chemical or thermal sensitivity in vi vo is not known. Here, we demonstrate that sensory neurons from mice lackin g VR1 are severely deficient in their responses to each of these noxious st imuli. VR1(-/-) mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detec tion of painful heat, and showed little thermal hypersensitivity in the set ting of inflammation. Thus, VR1 is essential for selective modalities of pa in sensation and for tissue injury-induced thermal hyperalgesia.