Nociceptive and Nonnociceptive Roles of TRPV3 and Its Druggability

Following the discovery of transient receptor potential vanilloid 1 (TRPV1), the founding member of the subfamily, knowledge accumulation on its biological roles in human pathology is being accelerated by its genetic, physiological, and pharmacological approaches. Owing to these scientific efforts, a series of its TRPV cousins have been found, and currently their characterizations are getting gradually active. TRPV3 was discovered as the last member a decade ago. To date, studies concerning TRPV3 revealed the distinct expression profiles in keratinocytes, extended modality to thermal and chemical insults, unique mode of sensitization, and intriguing phenotypes beyond sensory deficits when ablated. This knowledge has stimulated production of heterogeneous therapeutic hypotheses. However, in this 10th year of the TRPV3 cloning, substantial advances in TRPV3 pharmacological research is concentrated on nociception. This review not only focuses on the understanding of the pain pathology involving TRPV3 activation, but also highlights emerging information that is helping to define the roles of TRPV3 in skin defects. Multiple linkages between TRPV3 and other cellular and molecular signaling pathways are also discussed. Although the functions of TRPV3 in human physiology and disease still remain to be fully resolved at this point, insights gained from the present overview of outcomes from different fields may help unearth novel therapeutic implications and a better understanding of TRPV3 as a pharmacological target.