title: The cells and circuitry for itch responses in mice.
abstract: 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.
authors.affiliation: Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research/NIH, 49 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mishra
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hoon
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000378:metabolism / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D059225:Nociception; D054799:Phospholipase C beta; D011537:Pruritus / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000378:metabolism; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D002738:Chloroquine; D019332:Endothelin-1; D019886:Gastrin-Releasing Peptide; D006632:Histamine; D020097:Natriuretic Peptide, Brain; D054799:Phospholipase C beta; D017461:Receptors, Atrial Natriuretic Factor; D050916:TRPV Cation Channels; D000099242:Atrial Natriuretic Factor Receptor B; C493921:TRPV1 protein, mouse; C518040:Plcb3 protein, mouse