title: Abnormal activation of complement C3 in the spinal dorsal horn is closely associated with progression of neuropathic pain.
abstract: The aim of the present study was to investigate the role of complement activation in the pathogenesis of neuropathic pain (NPP) induced by peripheral nerve injury. We modified a classical chronic constriction injury (CCI) model (mCCI), and verified its reliability in rats. Furthermore, reverse transcription-PCR and immunohistochemistry were conducted to investigate complement activation in the spinal dorsal horn and the effect of a complement inhibitor, cobra venom factor (CVF), on the behavior of the mCCI model rats. We found that rats in the mCCI group presented a better general condition, without signs of autophagy of the toes. Moreover, mCCI induced a significant increase (+40%) in the expression of component 3 (C3) mRNA in the spinal dorsal horn, which was associated with hyperalgesia. Correlation analysis showed a negative correlation between the mechanical pain threshold and the expression of C3 in the spinal cord. Administration of CVF reduced the occurrence of hyperalgesia in mCCI rats and nearly reversed the hyperalgesia. In addition, the mCCI rats exhibited significantly less spinal superoxide dismutase activity and significantly greater levels of maleic dialdehyde compared to the sham-operated rats. Transmission electron micrographs revealed mitochondrial swelling, cell membrane damage, and cristae fragmentation in the neurons of the spinal dorsal horn 14 days after mCCI. Mitochondrial swelling was attenuated in mCCI rats receiving CVF. The findings demonstrated that abnormal complement activation occurred in the dorsal horn of the spinal cord in rats with NPP, and C3 in the spinal dorsal horn could play an important role in the cascade reaction of complements that are involved in the development of hyperalgesia.
authors.affiliation: Department of Pain Care and Nonvascular Intervention, Third Military Medical University, Chongqing, People's Republic of China. fachuannie1994@yahoo.com.cn
authors.forename: Fachuan
authors.initials: F
authors.lastname: Nie
authors.forename: Jinbao
authors.initials: J
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Su
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Jinmei
authors.initials: J
authors.lastname: Chen
authors.forename: Haihui
authors.initials: H
authors.lastname: Wang
authors.forename: Wanxiang
authors.initials: W
authors.lastname: Qin
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004546:Elapid Venoms / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D020671:Posterior Horn Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000447:Aldehydes; D003176:Complement C3; D004546:Elapid Venoms; D012333:RNA, Messenger; C016310:cobra venom factor; C015977:malealdehyde; D013482:Superoxide Dismutase