Activating, Inhibiting, and Highjacking TRP Channels for Relief from Itch

Abstract Itch (also known as pruritus) is an unpleasant sensation that triggers the desire to scratch. Unfortunately, chronic itch is a widespread problem, particularly among the elderly, and there are very few treatment options. Recently TRP channels have emerged as a therapeutic target for the treatment of itch. All sensory neurons that convey itch express TRPV1, and so defunctionalizing these neurons is likely to block itch. In addition, pruritogens activate metabotropic receptors that require TRPV1 and/or TRPA1 for signaling, suggesting that TRP channel antagonists may inhibit itch. Alternatively, TRPM8 agonists appear to activate endogenous anti-itch circuitry to block itch. Finally, active TRP channels can be highjacked to deliver a cell-impermeable sodium channel blocker, thereby selectively inactivating neurons that are pathologically activated in chronic itch. Thus, there are many promising mechanisms through which TRP channel modulation could be used as a therapeutic treatment for pruritus.