Kappa Opioid Receptor Distribution and Function in Primary Afferents

Publication date: 19 September 2018Source: Neuron, Volume 99, Issue 6Author(s): Lindsey M. Snyder, Michael C. Chiang, Emanuel Loeza-Alcocer, Yu Omori, Junichi Hachisuka, Tayler D. Sheahan, Jenna R. Gale, Peter C. Adelman, Elizabeth I. Sypek, Stephanie A. Fulton, Robert L. Friedman, Margaret C. Wright, Melissa Giraldo Duque, Yeon Sun Lee, Zeyu Hu, Huizhen Huang, Xiaoyun Cai, Kimberly A. Meerschaert, Vidhya Nagarajan, Toshiro HiraiSummaryPrimary 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. Th...

Source: Neuron - September 20, 2018 Category: Neuroscience Source Type: research