title: Adrenomedullin mediates tumor necrosis factor-α-induced responses in dorsal root ganglia in rats.
abstract: Adrenomedullin (AM), a member of the calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pain peptide. This study investigated the possible involvement of AM in tumor necrosis factor-alpha (TNF-α)-induced responses contributing to neuronal plasticity in the dorsal root ganglia (DRG). Exposure of the DRG explant cultures to TNF-α (5nM) for 48h upregulated the expression of AM mRNA. The treatment with TNF-α also increased the level of CGRP, CCL-2 and MMP-9 mRNA in the cultured DRG. This increase was attenuated by the co-treatment with the selective AM receptor antagonist AM22-52 (2μM). The blockade of AM receptors inhibited TNF-α-induced increase of the glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), phosphorylated cAMP response element binding protein (pCREB) and nuclear factor kappa B (pNF-κB) proteins. On the other hand, the treatment with the AM receptor agonist AM1-50 (10nM) for 96h induced an increase in the level of GFAP, IL-1β, pCREB and pNF-κB proteins. The inhibition of AM activity did not change TNF-α-induced phosphorylation of extracellular signal-related kinase (pERK) while the treatment with AM1-50 still increased the level of pERK in the cultured DRG. Immunofluorescence assay showed the colocalization of AM-like immunoreactivity (IR) with TNF-α-IR in DRG neurons. The present study suggests that the increased AM receptor signaling mediated the many, but not all, TNF-α-induced activities, contributing to peripheral sensitization in neuropathic pain.
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350117, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350117, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350117, China.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Huo
authors.affiliation: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350117, 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 350117, China. Electronic address: yhong@fjnu.edu.cn.
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058265:Receptors, Adrenomedullin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D017362:Cyclic AMP Response Element-Binding Protein; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D010446:Peptide Fragments; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D014409:Tumor Necrosis Factor-alpha; C108043:adrenomedullin (1-50); C104782:adrenomedullin (22-52); C081830:adrenomedullin receptor, rat; D053607:Adrenomedullin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9
keywords: Adrenomedullin (AM); Dorsal root ganglion (DRG); Extracellular signal-related kinase (ERK); Nuclear factor kappa B (NF-kB); Satellite cells; Tumor necrosis factor-alpha (TNF-α); cAMP-responsive element binding protein (CREB)