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Spinal Sirtuin 3 Contributes to Electroacupuncture Analgesia in Mice with Chronic Constriction Injury–Induced Neuropathic Pain

  • Yidan Zhang
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Caihong Lin
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Qingqing Yang
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Yuanzeng Wang
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Wen Zhao
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Lei Li
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
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  • Xiuhua Ren
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
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  • Jianyuan Zhao
    Affiliations
    Zhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
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  • Weidong Zang
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
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  • Jing Cao
    Correspondence
    Address correspondence to: Jing Cao, PhD, Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Number 100 Science Rd, Zhengzhou 450001, China.
    Affiliations
    Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
    Search for articles by this author

      Abstract

      Background

      Electroacupuncture (EA) is a traditional Chinese therapeutic technique that has a beneficial effect on neuropathic pain; however, the specific mechanism remains unclear. In this study, we investigated whether EA inhibits spinal Ca/calmodulin-dependent protein kinase II (CaMKIIα) phosphorylation through Sirtuin 3 (SIRT3) protein, thus relieving neuropathic pain.

      Materials and Methods

      We used wild-type and SIRT3 knockout (SIRT3−/−) mice and used chronic constriction injury (CCI) as a pain model. We performed Western blotting, immunostaining, von Frey, and Hargreaves tests to gather biochemical and behavioral data. Downregulation and overexpression and spinal SIRT3 protein were achieved by intraspinal injection of SIRT3 small interfering RNA and intraspinal injection of lentivirus-SIRT3. To test the hypothesis that CaMKIIα signaling was involved in the analgesic effects of EA, we expressed CaMKIIα-specific designer receptors exclusively activated by designer drugs (DREADDs) in the spinal dorsal horn (SDH) of mice.

      Results

      These results showed that the mechanical and thermal hyperalgesia induced by CCI was related to the decreased spinal SIRT3 expression in the SDH of mice. A significant reduction of mechanical and thermal thresholds was found in the SIRT3−/− mice. SIRT3 overexpression or EA treatment alleviated CCI-induced neuropathic pain and prevented the spinal CaMKIIα phosphorylation. Most importantly, EA increased the expression of spinal SIRT3 protein in the SDH. Downregulation of spinal SIRT3 or CaMKIIα Gq-DREADD activation inhibited the regulatory effect of EA on neuropathic pain.

      Conclusion

      Our results showed that CaMKIIα phosphorylation was inhibited by spinal SIRT3 in neuropathic pain and that EA attenuated CCI-induced neuropathic pain mainly by upregulating spinal SIRT3 expression in the SDH of mice.

      Keywords

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