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Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons.
Neuroscience. 2014 Jan 03; 256:178-94.N

Abstract

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu(31), Pro(34)]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu(31), Pro(34)]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu(31), Pro(34)]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [(35)S]GTPγS binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception.

Authors+Show Affiliations

Department of Physiology, School of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA. Electronic address: brad.taylor@uky.edu.Department of Physiology, School of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA.Division of Pharmacology, University of Missouri-Kansas City, Kansas City, MO, USA.Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.Veteran Affairs Greater Los Angeles Healthcare System and Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.Department of Physiology, School of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA.Department of Physiology and Biophysics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.Veteran Affairs Greater Los Angeles Healthcare System and Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24184981

Citation

Taylor, B K., et al. "Inflammation Enhances Y1 Receptor Signaling, Neuropeptide Y-mediated Inhibition of Hyperalgesia, and Substance P Release From Primary Afferent Neurons." Neuroscience, vol. 256, 2014, pp. 178-94.
Taylor BK, Fu W, Kuphal KE, et al. Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons. Neuroscience. 2014;256:178-94.
Taylor, B. K., Fu, W., Kuphal, K. E., Stiller, C. O., Winter, M. K., Chen, W., Corder, G. F., Urban, J. H., McCarson, K. E., & Marvizon, J. C. (2014). Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons. Neuroscience, 256, 178-94. https://doi.org/10.1016/j.neuroscience.2013.10.054
Taylor BK, et al. Inflammation Enhances Y1 Receptor Signaling, Neuropeptide Y-mediated Inhibition of Hyperalgesia, and Substance P Release From Primary Afferent Neurons. Neuroscience. 2014 Jan 3;256:178-94. PubMed PMID: 24184981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons. AU - Taylor,B K, AU - Fu,W, AU - Kuphal,K E, AU - Stiller,C-O, AU - Winter,M K, AU - Chen,W, AU - Corder,G F, AU - Urban,J H, AU - McCarson,K E, AU - Marvizon,J C, Y1 - 2013/10/31/ PY - 2013/09/27/received PY - 2013/10/21/revised PY - 2013/10/23/accepted PY - 2013/11/5/entrez PY - 2013/11/5/pubmed PY - 2014/8/29/medline KW - 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid KW - ANOVA KW - CFA KW - CGRP KW - DRG KW - G-protein KW - HEPES KW - IB4 KW - NK1R KW - NPY KW - PBS KW - RIA KW - SP KW - SP-LI KW - SP-like immunoreactivity KW - aCSF KW - analysis of variance KW - artificial cerebrospinal fluid KW - calcitonin gene-related peptide KW - capsaicin KW - complete Freund’s adjuvant KW - dorsal root ganglion KW - isolectin B4 KW - isolectin-B4 KW - neurokinin 1 receptor KW - neurokinin-1 receptor KW - neuropeptide Y KW - pain KW - phosphate-buffered saline KW - radioimmunoassay KW - substance P SP - 178 EP - 94 JF - Neuroscience JO - Neuroscience VL - 256 N2 - Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu(31), Pro(34)]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu(31), Pro(34)]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu(31), Pro(34)]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [(35)S]GTPγS binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24184981/Inflammation_enhances_Y1_receptor_signaling_neuropeptide_Y_mediated_inhibition_of_hyperalgesia_and_substance_P_release_from_primary_afferent_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00907-X DB - PRIME DP - Unbound Medicine ER -