Analgesic Potential of TRPV3 Antagonists

Regina      M. Reilly; Philip      R. Kym

Abstract

The vanilloid subfamily of transient receptor potential (TRPV) ion channels serves critical functions in sensory signaling in specialized cells and intact organisms ranging from yeast to primates. As thermosensors, chemosensors, and/or mechanosensors, these channels monitor the local environment and integrate and respond to multiple stimuli distinctively. More than a decade of research on the founding member of the subclass, TRPV1, has led to advancement of multiple antagonists into the clinic for the treatment of chronic pain. In recent years the comprehensive knowledge accessed through these studies has been applied to enhance understanding of other TRPV isoforms and, in particular, to determine whether they, too, represent promising targets for drug discovery. This review focuses on emerging data that define a role for TRPV3 in transducing signals in pain pathways and identify antagonists that demonstrate efficacy in relevant preclinical behavioral models.

Keywords: Antagonist, ion channel, pain, transient receptor potential, TRPV3, thermosensors, chemosensors, mechanosensors, multiple stimuli, multiple antagonists, chronic pain, TRPV isoforms, drug discovery, transducing signals in pain pathways, efficacy