The Cells and Circuitry for Itch Responses in Mice

• Published in: Science (American Association for the Advancement of Science) 2013-05, Vol.340 (6135), p.968-971
• Main Authors: Mishra, Santosh K., Hoon, Mark A.
• Format: Article
• Language: English
• Subjects: Animals; Chloroquine - pharmacology; Endothelin-1 - pharmacology; gastrin-releasing peptide; Gastrin-Releasing Peptide - metabolism; Gastrin-Releasing Peptide - pharmacology; Glass fiber reinforced plastics; Histamine - pharmacology; Histamines; Horns; Interneurons; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Natriuretic Peptide, Brain - genetics; Natriuretic Peptide, Brain - metabolism; Natriuretic Peptide, Brain - pharmacology; nerve fibers; Neurology; Neurons; Neuropeptides; Neuroscience; Neurotransmitters; Nociception; Peptides; Phospholipase C beta; Polypeptides; Pruritus - chemically induced; Pruritus - metabolism; Pruritus - physiopathology; Receptors; Receptors, Atrial Natriuretic Factor - metabolism; Rodents; Sensory neurons; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Signals; Spinal cord; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord - physiopathology; Switches; TRPV Cation Channels - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1233765

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.