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Regulated, electroporation-mediated delivery of pro-opiomelanocortin gene suppresses chronic constriction injury-induced neuropathic pain in rats

Gene Therapy volume 11, pages 933–940 (2004)Cite this article

Abstract

We previously reported that intrathecal pro-opiomelanocortin gene electroporation could reduce pain sensitivity induced by chronic constriction injury (CCI) of the sciatic nerve. For optimal use of antinociceptive gene therapy, it might be important to control the expression of the transfected gene extrinsically. For this purpose, a doxycycline-controlled transrepressor system composed of two plasmids coding, respectively, for pro-opiomelanocortin gene (pTRE2-POMC) and the silencer (pTel-off) was employed. The regulation of beta-endorphin expression was first assessed in spinal neuronal culture, then we electrotranfected this plasmid into the spinal cord of mononeuropathic rats and evaluated the analgesic potential of this therapy in vivo by thermal and mechanical withdrawal latency. Intraperitoneal injections of various doses of doxycycline were made to elucidate the possible exogenous downregulation of transfected beta-endorphin gene expression in vivo. The levels of beta-endorphin were analyzed by intrathecal microdialysis and radioimmunoassay. Intrathecal pTRE2-POMC/pTel-off electroporation elevated spinal beta-endorphin levels, as manifested in a significantly elevated pain threshold for chronic constriction injury limbs. Intraperitoneal doxycycline decreased the antinociceptive effect and spinal beta-endorphin levels in a dose-dependent manner. We concluded that intrathecal pTRE2-POMC/pTel-off electroporation alleviates CCI-induced limb pain, and can be controlled by intraperitoneal doxycycline administration.

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Acknowledgements

This work was supported by Grant No. 92-2314-B-182A-149- to Chung-Ren Lin from the National Science Council, Taipei, Taiwan.

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Authors and Affiliations

  1. Department of Biological Sciences, National Sun Yat-Sen University, Taiwan

    C-M Wu & J-T Cheng

  2. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan

    M-W Lin, Y-M Wang, Y-W Huang & C-R Lin

  3. Department of Anesthesiology, College of Medicine, National Taiwan University, Taiwan

    W-Z Sun & C-R Lin

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Wu, CM., Lin, MW., Cheng, JT. et al. Regulated, electroporation-mediated delivery of pro-opiomelanocortin gene suppresses chronic constriction injury-induced neuropathic pain in rats. Gene Ther 11, 933–940 (2004). https://doi.org/10.1038/sj.gt.3302244

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