@article{5f1a0ce8ee4d48588f95d8db1e1e0285,
title = "Kappa Opioid Receptor Distribution and Function in Primary Afferents",
abstract = "Primary afferents are known to be inhibited by kappa opioid receptor (KOR) signaling. However, the specific types of somatosensory neurons that express KOR remain unclear. Here, using a newly developed KOR-cre knockin allele, viral tracing, single-cell RT-PCR, and ex vivo recordings, we show that KOR is expressed in several populations of primary afferents: a subset of peptidergic sensory neurons, as well as low-threshold mechanoreceptors that form lanceolate or circumferential endings around hair follicles. We find that KOR acts centrally to inhibit excitatory neurotransmission from KOR-cre afferents in laminae I and III, and this effect is likely due to KOR-mediated inhibition of Ca2+ influx, which we observed in sensory neurons from both mouse and human. In the periphery, KOR signaling inhibits neurogenic inflammation and nociceptor sensitization by inflammatory mediators. Finally, peripherally restricted KOR agonists selectively reduce pain and itch behaviors, as well as mechanical hypersensitivity associated with a surgical incision. These experiments provide a rationale for the use of peripherally restricted KOR agonists for therapeutic treatment. Snyder et al. identify primary afferents that express the kappa opioid receptor in mouse and human and show that kappa opioid receptor signaling inhibits these cells in physiological and behavioral experiments.",
keywords = "DRG, Oprk1, dorsal root ganglia, dynorphin, human, itch, mouse, nalfurafine, pain, primary afferents",
author = "Snyder, {Lindsey M.} and Chiang, {Michael C.} and Emanuel Loeza-Alcocer and Yu Omori and Junichi Hachisuka and Sheahan, {Tayler D.} and Gale, {Jenna R.} and Adelman, {Peter C.} and Sypek, {Elizabeth I.} and Fulton, {Stephanie A.} and Friedman, {Robert L.} and Wright, {Margaret C.} and Duque, {Melissa Giraldo} and Lee, {Yeon Sun} and Zeyu Hu and Huizhen Huang and Xiaoyun Cai and Meerschaert, {Kimberly A.} and Vidhya Nagarajan and Toshiro Hirai and Gregory Scherrer and Kaplan, {Daniel H.} and Frank Porreca and Davis, {Brian M.} and Gold, {Michael S.} and Koerber, {H. Richard} and Ross, {Sarah E.}",
note = "Funding Information: We thank Dr. Makoto Tominga for the TRPM8 antibody, and the Penn Vector Core in the Gene Therapy Program of the University of Pennsylvania and the Sternson lab for provision of the original source material used to produce AAV9.CAGGS.Flex.ChR2-tdTomato.WPRE.SV40. Research reported in this publication was supported by NIH/NIAMS grants AR063772 and AR064445 (S.E.R.); NIH/NINDS grants NS023725 (H.R.K.), NS096705 (H.R.K.), NS092146 (L.M.S.), NS735483 (L.M.S.), NS083347 (M.S.G.), and NS07433 (K.A.M); NIH/NIDA grants DA034975 (F.P.), DA041809 (F.P.), and DA031777 (G.S.); NIH/NIDDK grant DK107966 (M.S.G.); NIH/NIBIB grant EBO21877 (B.M.D.); NIH/OD grant OD023859 (B.M.D.; M. Howard, PD); DoD Neurosensory Research Award MR130053 (G.S.); DoD National Defense Science and Engineering Graduate (NDSEG) Fellowship (E.I.S.); and Rita Allen Foundation/American Pain Society Awards (S.E.R. and G.S.). G.S. is a New York Stem Cell Foundation—Robertson Investigator. Funding Information: We thank Dr. Makoto Tominga for the TRPM8 antibody, and the Penn Vector Core in the Gene Therapy Program of the University of Pennsylvania and the Sternson lab for provision of the original source material used to produce AAV9.CAGGS.Flex.ChR2-tdTomato.WPRE.SV40. Research reported in this publication was supported by NIH/NIAMS grants AR063772 and AR064445 (S.E.R.); NIH/NINDS grants NS023725 (H.R.K.), NS096705 (H.R.K.), NS092146 (L.M.S.), NS735483 (L.M.S.), NS083347 (M.S.G.), and NS07433 (K.A.M); NIH/NIDA grants DA034975 (F.P.), DA041809 (F.P.), and DA031777 (G.S.); NIH/NIDDK grant DK107966 (M.S.G.); NIH/NIBIB grant EBO21877 (B.M.D.); NIH/OD grant OD023859 (B.M.D.; M. Howard, PD); DoD Neurosensory Research Award MR130053 (G.S.); DoD National Defense Science and Engineering Graduate (NDSEG) Fellowship (E.I.S.); and Rita Allen Foundation/American Pain Society Awards (S.E.R. and G.S.). G.S. is a New York Stem Cell Foundation?Robertson Investigator. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = sep,
day = "19",
doi = "10.1016/j.neuron.2018.08.044",
language = "English (US)",
volume = "99",
pages = "1274--1288.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}