Role of Transient Receptor Potential Channels in Acute and Chronic Itch

Members of the transient receptor potential (TRP) family have emerged as key players in itch transduction in the periphery. TRP family members are tetrameric cation selective channels that are expressed in diverse species, from flies to humans. The founding member of the TRP channel superfamily is TRP, a transduction channel required for light-evoked excitation of photoreceptors. In phototransduction, activation of the phospholipase C (PLC) pathway leads to the opening of TRP and its homolog TRP-L; flies lacking these channels display no light-evoked transduction currents and are blind. Over 27 members have since been identified in a variety of cell types and tissues (Figure 16.1). TRP channels are divided into seven subgroups based on protein homology rather than function: TRPC, TRPV, TRPM, TRPA, TRPN, TRPP, and TRPML. Generally, TRP channels function as polymodal cellular sensors involved in a wide variety of cellular processes. Many TRPs have been found to participate in sensory transduction pathways, including thermosensation, mechanosensation, taste, perception of pungent compounds, pheromone sensing, and osmolarity regulation. A number of excellent reviews describe the vast roles of TRP channels which will not be discussed. Here, we discuss the role of four TRP channels that have been proposed to play a role in itch transduction: TRPV1, TRPA1, TRPM8, and TRPV3. Historically, these four channels have been implicated in the transduction of noxious thermal, chemical, and/or mechanical stimuli, and more recent studies have implicated these channels in the transduction of itch.