Itch-inducing stimuli are detected by somatosensory neurons expressing the ion channel transient receptor potential V1 (TRPV1); however, the circuitry that mediates itch signalling has not yet been elucidated. Here, the authors showed that a subset of TRPV1 neurons express natriuretic polypeptide B (NPPB) and that loss of NPPB, or of its spinal receptor, specifically abolishes responses to itch-inducing agents in mice. They found that NPPB acts as a specific itch-related neurotransmitter to relay information from peripheral itch-sensitive neurons to the spinal cord.