Immunoneutralization of c-Fos using intrathecal antibody electroporation attenuates chronic constrictive injury-induced hyperalgesia and regulates preprodynorphin expression in rats

Chen Yu Lan, Ping Heng Tan, Jiin Tsuey Cheng, Hsiao Feng Lu, Ming Wei Lin, Po Ni Hsiao, Chung Ren Lin

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

摘要

Background: In vivo electroporation has been successfully used for the introduction of DNA, RNA, oligonucleotides, and proteins into cells for experimental and therapeutic purposes. The authors evaluated the efficacy of electroporation-mediated c-Fos antibody therapy for neuropathic pain in vitro and in vivo. Methods: First, the authors studied the inhibitory effects of intrathecal c-Fos antibody electroporation on the activating protein (AP-1) promoter activity in cultured spinal neuronal cells transfected with p-AP-Luc plasmid and activated with 100 μM glutamate. The inhibitory effect of c-Fos antibody electroporation in the regulation of AP-1 promoter activity was assessed according to the relative luciferase activity. Second, rats with chronic constrictive injury underwent electroporation treatment for neuropathic pain using c-Fos antibody. Thermal nociceptive thresholds were measured before chronic constrictive injury and then on even-numbered days, up to and including day 14, to assess and compare the therapeutic effects of intrathecal electroporation. The time course was assessed by Western blot analysis and by immunohistochemical analysis. Pronociceptive gene expression was measured by assessing prodynorphin mRNA and dynorphin peptides on days 2 and 10 after intrathecal c-Fos electroporation. Results: Cotransfection of c-Fos antibody significantly decreased glutamate-induced AP-1 activity. Intrathecal electrotransfer of c-Fos antibody attenuated spinal dynorphin levels, as manifested by significantly elevated pain thresholds in the chronic constrictive injury-affected limbs. Conclusion: This study shows that transfer of antibody into rat spinal cords by intrathecal electroporation is a useful method to study the function of endogenous factors of spinal-related disorders.

原文English
頁(從 - 到)938-946
頁數9
期刊Anesthesiology
99
發行號4
DOIs
出版狀態Published - 2003 10月 1

All Science Journal Classification (ASJC) codes

  • 麻醉與疼痛醫學

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