Figure 1.

Molecular identity of cold-sensitive afferents based upon the expression of TRPM8 and TRPA1. TRPM8 and TRPA1 are found in distinct and non-overlapping populations of sensory afferents, with TRPA1 expressed exclusively in some, but not all, neurons that express the heat-gated channel TRPV1. These thermosensitive TRP channels respond to a number of naturally occurring pungent compounds, such as menthol (mint), allyl isothiocyanate (mustard oil), cinnamaldehyde (cinnamon), and capsaicin ('hot' chili peppers), thus providing a molecular explanation for how these compounds provide distinct sensations of cold, heat, or spiciness. Based upon in vitro characterizations of these channels, along with their distinct expression patterns, thermal stimuli activating TRPM8-expressing afferents elicit the sensation of cool to potentially noxious cold, while TRPA1 afferents will merge both noxious cold and noxious heat, due to the expression of TRPV1.