Kappa Opioid Receptor Distribution and Function in Primary Afferents. Neuron 2018 Sep 19;99(6):1274-1288.e6
Date
09/22/2018Pubmed ID
30236284Pubmed Central ID
PMC6300132DOI
10.1016/j.neuron.2018.08.044Scopus ID
2-s2.0-85053011653 (requires institutional sign-in at Scopus site) 112 CitationsAbstract
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.
Author List
Snyder LM, Chiang MC, Loeza-Alcocer E, Omori Y, Hachisuka J, Sheahan TD, Gale JR, Adelman PC, Sypek EI, Fulton SA, Friedman RL, Wright MC, Duque MG, Lee YS, Hu Z, Huang H, Cai X, Meerschaert KA, Nagarajan V, Hirai T, Scherrer G, Kaplan DH, Porreca F, Davis BM, Gold MS, Koerber HR, Ross SEAuthor
Tayler D. Sheahan PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAxons
Mice
Mice, Transgenic
Neurons
Neurons, Afferent
Nociceptors
Pain
Pain Management
Receptors, Opioid, kappa
Signal Transduction
