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Spinal Serotonin 1A Receptor Contributes to the Analgesia of Acupoint Catgut Embedding by Inhibiting Phosphorylation of the N-Methyl-d-Aspartate Receptor GluN1 Subunit in Complete Freund's Adjuvant-Induced Inflammatory Pain in Rats

  • Author Footnotes
    1 W.-Q.C. and W.-S.S. contributed equally to this work.
    Wen-Qiang Cui
    Footnotes
    1 W.-Q.C. and W.-S.S. contributed equally to this work.
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
    Search for articles by this author
  • Wen-Shan Sun
    Affiliations
    Department of Traditional Chinese Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
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  • Fei Xu
    Affiliations
    The Institute of Integrative Medicine, Fudan University, Shanghai, China

    Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
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  • Xue-Ming Hu
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
    Search for articles by this author
  • Wei Yang
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Yang Zhou
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Li-Xia Du
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Wen-Wen Zhang
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Qi-Liang Mao-Ying
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Wen-Li Mi
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
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  • Author Footnotes
    2 Y.-X.C. and Y.-Q.W. are co-corresponding authors of this work.
    Yu-Xia Chu
    Correspondence
    Address reprint requests to Yu-Xia Chu, 130 Dong'an Road, Shanghai 200032, China.
    Footnotes
    2 Y.-X.C. and Y.-Q.W. are co-corresponding authors of this work.
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
    Search for articles by this author
  • Yan-Qing Wang
    Correspondence
    Address reprint requests to Yan-Qing Wang, Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University. 130 Dong'an Road, Xuhui District, Shanghai 200032, PR China.
    Affiliations
    Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    The Institute of Integrative Medicine, Fudan University, Shanghai, China
    Search for articles by this author
  • Author Footnotes
    1 W.-Q.C. and W.-S.S. contributed equally to this work.
    2 Y.-X.C. and Y.-Q.W. are co-corresponding authors of this work.
Published:August 10, 2018DOI:https://doi.org/10.1016/j.jpain.2018.07.011

      Abstract

      Acupoint catgut embedding (ACE) is a widely used traditional Chinese medicine method to manage various diseases, including chronic inflammatory pain. We sought to assess the possible analgesic effects of ACE in comparison with electroacupuncture (EA) and to study the analgesic mechanisms of ACE in a rat model of inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into the hind paw of rats. The von Frey, radiant heat, and gait analysis tests were performed to evaluate the analgesic effects of ACE and EA, and Western blot and immunohistochemistry assays were carried out to determine the molecular mechanisms of ACE. ACE treatments were administered every 4 days or every week with different acupoints (ipsilateral, contralateral, or bilateral ST36 and GB30 acupoints). The most effective ACE strategy for attenuating the nocifensive response induced by CFA injection was performing ACE once a week at ipsilateral ST36 in combination with GB30. EA treatment every other day at ipsilateral ST36 and GB30 showed comparable analgesic effects. ACE inhibited the increased activation of the GluN1 subunit of the N-methyl-d-aspartate receptor and the subsequent Ca2+-dependent signals (CaMKII, ERK, and CREB) that take place in response to CFA. The effects of ACE were similar to intrathecal injection of vilazodone (a serotonin 1A receptor [5-HT1AR] agonist) and were blocked by WAY-100635 (a 5-HT1AR antagonist). In summary, we show that ACE attenuates CFA-induced inflammatory pain in rats by activating spinal 5-HT1AR and by inhibiting the phosphorylation of GluN1, thus, inhibiting the activation of Ca2+-dependent signaling cascades.

      Perspective

      This article presents the novel evidence concerning the spinal 5-HT1AR activation-related molecular signaling of ACE analgesia in a rat model of CFA-induced inflammatory pain. This work may help clinicians to verify the effectiveness of ACE analgesia and to better understand the underlying mechanism.

      Key words

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