title: Intrathecal 5-azacytidine inhibits global DNA methylation and methyl- CpG-binding protein 2 expression and alleviates neuropathic pain in rats following chronic constriction injury.
abstract: The pathogenesis of neuropathic pain remains largely unknown. Epigenetic mechanisms may play a major role in regulating expression of pro- or antinociceptive genes. DNA methylation is a major epigenetic mechanism in vertebrates, and methyl- CpG-binding protein 2 (MeCP2) is directly involved in methylation-mediated gene silencing. To determine how changes in global DNA methylation and MeCP2 expression occur following chronic constriction injury (CCI) and how repression of DNA methylation affects these changes and attenuates neuropathic pain, we used intrathecal 5-azacytidine, a DNA methyltransferase inhibitor, in CCI rats. Rats received 0.9% saline or 5-azacytidine (10μmol·d(-1)) via spinal injection once daily from day 3 to day 14 after CCI surgery. Global DNA methylation and MeCP2 expression increased in the spinal cord in CCI rats on day 14 after CCI surgery. Mechanical allodynia and thermal hyperalgesia induced by CCI were attenuated by intrathecal 5-azacytidine from day 5 to day 14 after CCI surgery. The increases in global DNA methylation and MeCP2 expression in the spinal cord in CCI rats were also significantly inhibited by intrathecal 5-azacytidine. These results demonstrate that increased global DNA methylation and MeCP2 expression in the spinal cord after nerve damage may play an important role in neuropathic pain. 5-azacytidine shows potential for treating neuropathic pain.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central-South University, Hunan 410008, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Qu-Lian
authors.initials: QL
authors.lastname: Guo
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Yan
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhu
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Huang
authors.forename: Wang-Yuan
authors.initials: WY
authors.lastname: Zou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage*; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000150:complications; D019175:DNA Methylation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D001374:Azacitidine