Steps Filled In Along Itch Pathway

How stimuli, such as bug bites, cause the brain to register “itch” versus “pain” has puzzled scientists for decades. Researchers have long debated whether the two sensations share nerve cell circuitry or whether they have independent signaling pathways. Santosh K. Mishra and Mark A. Hoon of the National Institutes of Health recently tipped the scales in the latter direction when they demonstrated that a neurotransmitter called natriuretic polypeptide b (Nppb) specifically signals itch (Science 2013, DOI: 10.1126/science.1233765). The researchers found that mice genetically engineered to lack Nppb didn’t scratch in response to a host of itch-causing agents, including histamine. But when Nppb was injected into the spinal cords of the mutant mice, the animals scratched vigorously. These mice also responded normally to pain-inducing stimuli. The duo proposes that sensory neurons innervating the skin and other tissue secrete Nppb after being activated by an itch-causing substance. The peptide then triggers a secondary set of neurons in the spinal cord by binding to an embedded protein receptor, Npra. Because Nppb and Npra also play a role in heart function, it remains unclear whether they are viable drug targets, Hoon says, but these results are a step in the direction of switching off chronic itch.