title: Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury.
abstract: Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3μg/15μl, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats.
authors.affiliation: Department of Clinical Pharmacology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.|Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.|Department of Anesthesiology and Pain Medicine, School of Medicine, Wonkwang University, Iksan, Korea.
authors.forename: Yong-Kwan
authors.initials: YK
authors.lastname: Cheong
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
authors.forename: Shao-Qiu
authors.initials: SQ
authors.lastname: He
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Tiwari
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
authors.affiliation: Department of Clinical Pharmacology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Jinheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism; D015536:Down-Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D007278:Injections, Spinal; D008161:Lumbosacral Region; D008297:Male; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries*; D014110:Touch; D000097004:Gap Junction delta-2 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000097004:Gap Junction delta-2 Protein; C580592:Gja1 protein, rat
keywords: Connexin 43; Gap junction; Glia; Neuropathic pain