Transient Receptor Potential Channels and Pruritus

Itch induction and allergy development are regulated by highly complex pathways that involve dynamic cross-talk events between cells within the skin. These include the transient receptor potential (TRP) ion channels. For example, the intensity, quality, and the clinical characteristics of itch, pain, and inflammatory sensations can be influenced by thermal stimuli within the activation range of thermo-sensitive TRP cannels. The thermo-TRP channel TRPV1 contributes to the regulation of the skin surface temperature which has a major impact on the epidermal permeability barrier. TRPV1 has an important role in the induction of histamine-mediated pruritus in sensory neurons while TRPV4 has a role to play in histamine-independent itch induction. The stimulation of TRPV2 on mast cells provokes pro-inflammatory degranulation events and subsequent release of histamine, thus directly promoting the induction of itch. TRPV3 is likely to have a crucial function in epidermal barrier formation and hair morphogenesis. TRPM8 and TRPA1 interfere with the induction of sensory sensations. Cutaneously expressed temperature sensors of the TRP channel family thus became an attractive target for pharmacological treatment of pruritic, inflammatory, and nociceptive processes.