Abnormal Somatosensory Behaviors Associated With a Gain-of-Function Mutation in TRPV3 Channels.

Thermosensitive transient receptor potential V3 (TRPV3) is a polymodal receptor implicated in nociceptive, thermoceptive, pruritoceptive, and inflammatory pathways. Reports focused on understanding the role of TRPV3 in thermoception or nociception are not conclusive. Previous studies also show that aberrant hyperactivity of TRPV3 channels results in spontaneous itch and dermatitis-like symptoms, but the resultant behavior is highly dependent on the background of the animal and the skin microbiome. To determine the function of hyperactive TRPV3 channels in somatosensory sensations, we tested different somatosensory behaviors using a genetic mouse model that carries a gain-of-function point mutation in the gene ( ). Here we report that mutants show reduced perception of cold, acetone-induced cooling, punctate, and sharp mechanical pain. By contrast, locomotion, noxious heat, touch, and mechanical itch are unaffected in mice. We fail to observe any spontaneous itch responses and/or dermatitis in mutants under specific pathogen ()-free conditions. However, we find that the scratching events in response to various pruritogens are dramatically decreased in mice in comparison to wild-type littermates. Interestingly, we observe sensory hypoinnervation of the epidermis in mutants, which might contribute to the deficits in acute mechanical pain, cool, cold, and itch sensations.