title: Effect of Mas-related gene (Mrg) receptors on hyperalgesia in rats with CFA-induced inflammation via direct and indirect mechanisms.
abstract: OBJECTIVE
  Mas oncogene-related gene (Mrg) receptors are exclusively distributed in small-sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms.
  
  
  METHODS
  A selective MrgC receptor agonist, bovine adrenal medulla peptide 8-22 (BAM8-22) or melanocyte-stimulating hormone (MSH) or the μ-opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT-PCR.
  
  
  RESULTS
  CFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8-22 or MSH, given i.t., generated instant short and delayed long-lasting attenuations of CFA-induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up-regulation of neuronal NOS (nNOS), CGRP and c-Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8-22 of delayed anti-hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8-22 also increased mRNA for MORs and pro-opiomelanocortin, along with β-endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co-localized in DRG neurons.
  
  
  CONCLUSIONS
  Activation of MrgC receptors suppressed up-regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up-regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could 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, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jiang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhou
authors.forename: Yuping
authors.initials: Y
authors.lastname: Huo
authors.forename: Tingjun
authors.initials: T
authors.lastname: Chen
authors.forename: Fenjuan
authors.initials: F
authors.lastname: Hu
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013004:Somatostatin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000700:Analgesics; C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017450:Receptors, Opioid, mu; C571042:bovine adrenal medulla 8-22; D013004:Somatostatin; D009074:Melanocyte-Stimulating Hormones; D005620:Freund's Adjuvant; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015740:Calcitonin Gene-Related Peptide
keywords: Mas-related gene (Mrg) receptors; dorsal root ganglia (DRG); inflammatory hyperalgesia; spinal dorsal horn; μ-opioidergic activity
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