The Cells and Circuitry for Itch Responses in Mice

See allHide authors and affiliations

Science  24 May 2013:
Vol. 340, Issue 6135, pp. 968-971
DOI: 10.1126/science.1233765

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

The Master Switch for Itch?

Recently, gastrin-releasing peptide (GRP) has been implicated as the primary neurotransmitter between itch-sensitive nerve fibers and downstream neurons in the spinal cord. However, Mishra and Hoon (p. 968) challenge this view, provide evidence that natriuretic polypeptide b (Nppb) is the central itch neurotransmitter, and suggest that GRP is released by second-order neurons in the spinal dorsal horn that express the Nppb receptor and are excited by Nppb.


Itch is triggered by somatosensory neurons expressing the ion channel TRPV1 (transient receptor potential cation channel subfamily V member 1), but the mechanisms underlying this nociceptive response remain poorly understood. Here, we show that the neuropeptide natriuretic polypeptide b (Nppb) is expressed in a subset of TRPV1 neurons and found that Nppb−/− mice selectively lose almost all behavioral responses to itch-inducing agents. Nppb triggered potent scratching when injected intrathecally in wild-type and Nppb−/− mice, showing that this neuropeptide evokes itch when released from somatosensory neurons. Itch responses were blocked by toxin-mediated ablation of Nppb-receptor–expressing cells, but a second neuropeptide, gastrin-releasing peptide, still induced strong responses in the toxin-treated animals. Thus, our results define the primary pruriceptive neurons, characterize Nppb as an itch-selective neuropeptide, and reveal the next two stages of this dedicated neuronal pathway.

View Full Text

Stay Connected to Science