Scratching the surface: a role of pain-sensing TRPA1 in itch.

摘要

The molecular mechanisms of itch, particularly histamine-independent itch, are unclear. Wilson et al. report that TRPA1, an ion channel critical for pain sensation, also functions as an essential component of itch transduction. Itch, or pruritus, is defined as an unpleasant sensation that evokes a desire or reflex to scratch and that consequently serves as a self-protective mechanism to help preserve the body from irritating insults . However, itch associated with many skin, systemic and nervous system disorders can be debilitating and represents an unmet clinical need . Itch can be evoked by diverse mediators, collectively known as pruritogens. The best-known pruritogen is histamine, which is released mainly by skin mast cells in response to external stimuli such as a mosquito bite and acts through G protein-coupled histamine receptors present on a subset of sensory neurons. Histamine-dependent itch in humans can be effectively blocked by histamine receptor antagonists. By contrast, most pathophysiologi-cally relevant itch is insensitive to blockers of the histamine pathway, indicating the existence of distinct pruritogens and itch pathways. Such histamine-independent pruritogens include the antimalarial drug chloroquine and the endogenous pruritogen BAM8-22 (ref. 2). A recent study identified Mrgpr A3 and MrgprC11, two members of the Mas-related G protein-coupled receptor (Mrgpr), as itch receptors for chloroquine and BAM8-22, respectively . However, the downstream signaling mechanism underlying Mrgpr A3- and MrgprC11-mediated itch remained unknown. In this issue of Nature Neuroscience, a study reported by Wilson et al. demonstrates that TRPA1, a polymodal noclsensor, serves as a transduction ion channel for histamine-independent itch .