title: Reversal of neurochemical alterations in the spinal dorsal horn and dorsal root ganglia by Mas-related gene (Mrg) receptors in a rat model of spinal nerve injury.
abstract: The rodent Mas-related gene (Mrg) receptor subtype C has been demonstrated to inhibit pathological pain. This study investigated the mechanisms underlying the reversal of pain hypersensitivity by the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) in a rat model of L5 spinal nerve ligation (SNL). Intrathecal (i.t.) administration of BAM8-22 (0.1-10nmol) attenuated mechanical allodynia in a dose-dependent manner on day 10 after SNL. The antiallodynia effect of BAM8-22 was abolished by MrgC receptor antibody, but not by naloxone. I.t. BAM8-22 (10nmol) inhibited SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) and phosphorylation of cyclic AMP response element-binding protein (p-CREB) in the spinal dorsal horn. The BAM8-22 treatment reversed the SNL-induced astrocyte activation, increase of interleukin-1β (IL-1β) expression and phosphorylation of extracellular signal-regulated kinase (p-ERK) in the spinal cord. BAM8-22 also reversed the upregulation of fractalkine and IL-1β in small- and medium-sized dorsal root ganglion (DRG) neurons. Furthermore, the BAM8-22 exposure suppressed the lipopolysaccharide (LPS)-induced increase of nNOS and IL-1β in the DRG explant cultures and the BAM8-22-induced suppression disappeared in the presence of MrgC receptor antibody. The present study provides evidence that activation of MrgC receptors inhibits nerve injury-induced increase of pronociceptive molecules in DRG neurons, suppressing astrocyte activation, the upregulation of excitatory mediators and phosphorylation of transcription factors in the spinal dorsal horn. As MrgC receptors are unequally expressed in the dorsal root and trigeminal ganglia, this study suggests that targeting MrgC receptors could be a new therapy for neuropathic pain with limited unwanted effects.
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China.
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, 3501117, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xue
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Yan
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Lin
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Huang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian, 3501117, China. Electronic address: yhong@fjnu.edu.cn.
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D043562:Receptors, G-Protein-Coupled; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Astrocytes; Central sensitization; Dorsal root ganglion (DRG); Mas-related gene (Mrg) receptor; Neuropathic pain, Spinal dorsal horn