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Abnormal activation of complement C3 in the spinal dorsal horn is closely associated with progression of neuropathic pain

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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.
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Document Type: Research Article

Affiliations: 1: Department of Pain Care and Nonvascular Intervention, The First Subordinate Hospital, Third Military Medical University, Chongqing, P.R. China 2: Department of Anesthesiology, Bethune Peace Hospital, Shijiazhuang, Hebei, P.R. China 3: Department of Anesthesiology, The First Subordinate Hospital, Third Military Medical University, Chongqing, P.R. China 4: Department of Anesthesiology, University Hospital of Brussels (UZ Brussel), Brussels, Belgium

Publication date: January 1, 2013

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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