Molecular and cellular mechanisms of trigeminal chemosensation

Abstract

Three sensory systems, olfaction, taste, and somatosensation, are dedicated to the detection of chemicals in the environment. Trigeminal somatosensory neurons enable us to detect a wide range of environmental stimuli, including pressure, temperature, and chemical irritants, within the oral and nasal mucosa. Natural plant-derived irritants have served as powerful pharmacological tools for identifying receptors underlying somatosensation. This is illustrated by the use of capsaicin, menthol, and wasabi to identify the heat-sensitive ion channel TRPV1, the cold-sensitive ion channel TRPM8, and the irritant receptor TRPA1, respectively. In addition to TRP channels, members of the two-pore potassium channel family have also been implicated in trigeminal chemosensation. KCNK18 was recently identified as a target for hydroxy-alpha-sanshool, the tingling and numbing compound produced in Schezuan peppers and other members of the Xanthoxylum genus. The role of these channels in trigeminal thermosensation and pain will be discussed.

Figure 1

Schematic of natural plant products and their cognate receptors. Extracts from the fruits of the Capsicum genus contain capsaicin, an agonist of TRPV1. Leaves from the Mentha genus contain high concentrations of menthol, an agonist of TRPM8. Allicin is the primary pungent compound found in garlic and is one of many TRPA1 agonists. Hydroxy-α-sanshool, the numbing compound in prickly ash, inhibits KCNK3, 9, and 18 potassium channels. (In color in Annals online.)