Publication Date:
2013-05-25
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670709/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670709/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mishra, Santosh K -- Hoon, Mark A -- ZIA DE000721-04/Intramural NIH HHS/ -- ZIA DE000721-05/Intramural NIH HHS/ -- ZIA DE000721-06/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 24;340(6135):968-71. doi: 10.1126/science.1233765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research/NIH, 49 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704570" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Chloroquine/pharmacology
;
Endothelin-1/pharmacology
;
Gastrin-Releasing Peptide/metabolism/pharmacology
;
Histamine/pharmacology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Natriuretic Peptide, Brain/genetics/*metabolism/pharmacology
;
*Nociception
;
Phospholipase C beta
;
Pruritus/chemically induced/metabolism/*physiopathology
;
Receptors, Atrial Natriuretic Factor/metabolism
;
Sensory Receptor Cells/drug effects/*metabolism
;
Spinal Cord/drug effects/pathology/physiopathology
;
TRPV Cation Channels/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics