title: Effects of dexmedetomidine on P2X4Rs, p38-MAPK and BDNF in spinal microglia in rats with spared nerve injury.
abstract: Microglia in the spinal cord is evidenced to play a crucial role in neuropathic pain. Spinal P2X4 receptors (P2X4Rs), which are mainly expressed in microglia, have been investigated for their roles in neuropathic pain. Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, is clinically applied to sedation and analgesia. Despite the proposed mechanisms underlying DEX-induced analgesia, the possible interactions between DEX and P2X4Rs at a molecular level have not been elucidated. We designated the spared nerve injury (SNI) to establish the neuropathic pain model. Mechanical paw withdrawal threshold (MWT) was measured to evaluate the sensitivity of neuropathic pain in rats. MWT was significantly decreased in SNI rats versus control rats. Expressions of spinal P2X4Rs, phosphorylated p38-mitogen-activated protein kinase (p-p38-MAPK) and brain-derived neurotrophic factor (BDNF) were upregulated in SNI rats. Immunofluorescence assay indicated higher densities of microglia and P2X4Rs, which appeared yellow in colour, suggesting they were co-labelled. Intraperitoneal injections of DEX 40μg/kg for 14 consecutive days markedly reversed the SNI-induced decline of MWT; the activation of microglia was markedly inhibited; in addition, the protein expressions of P2X4Rs, p-p38-MAPK and BDNF were significantly downregulated. Thus, DEX could attenuate the neuropathic pain in SNI rats, of which the mechanism might be related to the down-expressed P2X4Rs, p-p38 and BDNF in microglia of spinal dorsal horn.
authors.affiliation: Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: zhoutt0326@163.com.
authors.forename: Tian-tian
authors.initials: TT
authors.lastname: Zhou
authors.affiliation: Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: wujingr5810@sina.com.
authors.forename: Jing-ru
authors.initials: JR
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: chenzy0627@126.com.
authors.forename: Zi-yang
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: shu.19890621@163.com.
authors.forename: Zhen-xiu
authors.initials: ZX
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: kevinpsd@gmail.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Miao
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D019208:Brain-Derived Neurotrophic Factor; D006993:Hypnotics and Sedatives; D058848:Receptors, Purinergic P2X4; D020927:Dexmedetomidine; D048051:p38 Mitogen-Activated Protein Kinases
keywords: BDNF; Dexmedetomidine; Microglia; Neuropathic pain; P2X4Rs; Spinal cord; p-p38-MAPK