Molecular basis of peripheral innocuous warmth sensitivity

The perception of innocuous warmth is a sensory capability that facilitates thermoregulatory, social, hedonic, and even predatory functions. It has long been recognized that innocuous warmth perception is triggered by activation of a subpopulation of specially tuned peripheral thermosensory neurons. In addition, there is growing evidence that thermotransduction by nonneuronal cells, such as skin keratinocytes, might contribute to or modulate our thermosensory experience. Yet, the precise molecular mechanisms underlying warmth transduction are only now being uncovered. Recent molecular genetics approaches have led to the identification of multiple candidate warmth-transducing molecules that appear to confer thermosensitivity upon innocuous warmth afferents and/or neighboring cell types. Most, but not all, of these candidate transducers are members of the transient receptor potential (TRP) ion channel family. Among the latter, evidence supporting a function in innocuous warmth sensation is strongest for TRPV1 and TRPM2 in mammals and for TRPA1 in nonmammalian species.