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RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal projection neurons express the neurokinin-1 receptor (Tacr1), and ON-cells are excited by local administration of substance P (SP). We hypothesized that Tacr1-expressing RVM ON cells exert an inhibitory effect on itch opposite to their pronociceptive action. Intramedullary microinjection of SP significantly potentiated RVM ON cells and reduced pruritogen-evoked scratching while producing mild mechanical sensitization. Chemogenetic activation of RVM Tacr1-expressing RVM neurons also reduced acute pruritogen-evoked scratching. Optotagging experiments confirmed RVM Tacr1-expressing neurons to be ON cells. We conclude that Tacr1-expressing ON cells in RVM play a significant role in the modulation of pruriceptive transmission.<\/jats:p>","DOI":"10.7554\/elife.69626","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T06:15:56Z","timestamp":1659680156000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69626","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-9324","authenticated-orcid":true,"given":"Taylor","family":"Follansbee","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurobiology, Physiology and Behavior, University of California, Davis","place":["Davis, United 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