Nppb Neurons Are Sensors of Mast Cell-Induced Itch

摘要

Itch is an unpleasant skin sensation that can be triggeredby exposure to many chemicals, includingthose released by mast cells. The natriuretic polypeptideb (Nppb)-expressing class of sensory neurons,when activated, elicits scratching responses inmice, but it is unclear which itch-inducing agentsstimulate these cells and the receptors involved.Here, we identify receptors expressed by Nppb neuronsand demonstrate the functional importance ofthese receptors as sensors of endogenous pruritogensreleased by mast cells. Our search for receptorsin Nppb neurons reveals that they express leukotriene,serotonin, and sphingosine-1-phosphate receptors.Targeted cell ablation, calcium imaging ofprimary sensory neurons, and conditional receptorknockout studies demonstrate that these receptorsinduce itch by the direct stimulation of Nppb neuronsand neurotransmission through the canonical gastrinreleasingpeptide (GRP)-dependent spinal cord itchpathway. Together, our results define a molecularand cellular pathway for mast cell-induced itch.