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- W2597667020 endingPage "S27" @default.
- W2597667020 startingPage "S27" @default.
- W2597667020 abstract "Peripherally selective kappa opioids are emerging as a novel treatment for pain and itch that have shown efficacy in several recent clinical trials. Yet, the subtypes of somatosensory neurons that express KOR remain unclear. Using a newly developed KOR-cre knockin allele, viral tracing, and single-cell PCR we reveal that that KOR is expressed in a specific subset of peptidergic afferents that are tuned for inflammatory pain and itch, but not heat or mechanical force. Consistent with this, peripherally restricted KOR agonists inhibit behavioral responses to chemical pain and itch, but not acute heat responses nor punctuate mechanical sensitivity. Unexpectedly, we also find that KOR is expressed in subsets of primary afferents that form lanceolate or circumferential endings around hair follicles, suggesting an unappreciated role for KOR signaling in the modulation of low-threshold mechanosensation. At a functional level, optogenetic experiments reveal that dynorphin inhibits glutamate release from the central terminals of KOR-expressing afferents, and genetically-labeled afferents show inhibited calcium influx in response to kappa agonists. These experiments provide key insight for the rationale use of peripherally selective KOR agonists for the modulation of inflammatory pain, itch, and potentially mechanical allodynia." @default.
- W2597667020 created "2017-04-07" @default.
- W2597667020 creator A5009507330 @default.
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- W2597667020 date "2017-04-01" @default.
- W2597667020 modified "2023-09-27" @default.
- W2597667020 title "(206) Modulation of multiple modalities of somatosensory information by peripheral kappa opioid receptors" @default.
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