title: Activation of Mas Oncogene-Related G Protein-Coupled Receptors Inhibits Neurochemical Alterations in the Spinal Dorsal Horn and Dorsal Root Ganglia Associated with Inflammatory Pain in Rats.
abstract: Mas oncogene-related G protein-coupled receptor C (MrgC) is unequally expressed in sensory ganglia and has been shown to modulate pathologic pain. This study investigated the mechanism underlying the effect of MrgC receptors on inflammatory pain. Intrathecal administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) (30 nmol) inhibited complete Freund's adjuvant-evoked hyperalgesia. This was associated with the inhibition of protein kinase C-γ and phosphorylated extracellular signal-regulated protein kinase in the spinal cord and/or dorsal root ganglia (DRG). The complete Freund's adjuvant injection in the hindpaw induced an increase in Gq, but not Gi and Gs, protein in the spinal dorsal horn. This increase was inhibited by the intrathecal administration of BAM8-22. The exposure of DRG cultures to bradykinin (10 μM) and prostaglandin E2 (1 μM) increased the expression of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase in small- and medium-sized neurons as well as the levels of CGRP, aspartate, and glutamate in the cultured medium. The bradykinin/prostaglandin E2-induced alterations were absent in the presence of BAM8-22 (10 nM). These results suggest that the activation of MrgC receptors can modulate the increase in the expression of CGRP and neuronal nitric oxide synthase as well as the release of CGRP and excitatory amino acids in DRG associated with inflammatory pain. This modulation results in the inhibition of pain hypersensitivity by suppressing the expression of Gq protein and protein kinase C-γ and extracellular signal-regulated protein kinase signaling pathways in the spinal cord and/or DRG. The present study suggests that MrgC receptors may be a novel target for relieving inflammatory pain.
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.).
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.).
authors.forename: Peizhong
authors.initials: P
authors.lastname: Wang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.).
authors.forename: Jianping
authors.initials: J
authors.lastname: Jiang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.).
authors.forename: Qingqin
authors.initials: Q
authors.lastname: Lv
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.).
authors.forename: Xueai
authors.initials: X
authors.lastname: Zeng
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University , Fuzhou, Fujian, China (D.W., P.W., J.J., Q.L., Y.H.); and Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, China (X.Z.) yhong@fjnu.edu.cn.
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism*
chemical_list: C000591603:Mrgprc protein, rat; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C571042:bovine adrenal medulla 8-22; D005620:Freund's Adjuvant; C087857:protein kinase C gamma; D011493:Protein Kinase C; D015232:Dinoprostone; D001920:Bradykinin