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Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions

  • Seungtae Kim
    Affiliations
    Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina

    Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea
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  • Xin Zhang
    Affiliations
    Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina

    Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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  • Sandra C. O'Buckley
    Affiliations
    Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina
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  • Mary Cooter
    Affiliations
    Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
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  • Jongbae J. Park
    Affiliations
    Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina
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  • Andrea G. Nackley
    Correspondence
    Address reprint requests to Andrea G. Nackley, PhD, Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, 905 South LaSalle Street #1010, Durham, NC 27710.
    Affiliations
    Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina
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      Highlights

      • Sustained inhibition of catechol-O-methyltransferase led to persistent pain and neuroinflammation in mice.
      • ST36, but not sham, acupuncture alleviated pain.
      • ST36 acupuncture reduced spinal phosphorylated p38 expression and astrocyte activation.
      • The magnitude of the analgesic response was greater in rapid-healing MRL/MpJ mice.

      Abstract

      Patients with chronic overlapping pain conditions have decreased levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Consistent with clinical syndromes, we previously demonstrated that COMT inhibition in rodents produces persistent pain and heightened immune responses. Here, we sought to determine the efficacy of manual acupuncture in resolving persistent pain and neuroinflammation in the classic inbred C57BL/6 strain and the rapid-wound healing MRL/MpJ strain. Mice received subcutaneous osmotic minipumps to deliver the COMT inhibitor OR486 or vehicle for 13 days. On day 7 after pump implantation, acupuncture was performed at the Zusanli (ST36) point or a non-acupoint for 6 consecutive days. Behavioral responses to mechanical stimuli were measured throughout the experiment. Immunohistochemical analysis of spinal phosphorylated p38 mitogen-activated protein kinase, a marker of inflammation, and glial fibrillary acidic protein, a marker of astrogliosis, was performed on day 13. Results demonstrated that ST36, but not sham, acupuncture resolved mechanical hypersensitivity and reduced OR486-dependent increases in phosphorylated p38 and glial fibrillary acidic protein in both strains. The magnitude of the analgesic response was greater in MRL/MpJ mice. These findings indicate acupuncture as an effective treatment for persistent pain linked to abnormalities in catecholamine signaling and, furthermore, that analgesic efficacy may be influenced by genetic differences.

      Perspective

      Chronic overlapping pain conditions remain ineffectively managed by conventional pharmacotherapies. Here, we demonstrate that acupuncture alleviates persistent pain and neuroinflammation linked to heightened catecholaminergic tone. Mice with superior healing capacity exhibit greater analgesic efficacy. Findings indicate acupuncture as an effective treatment for chronic overlapping pain conditions and provide insight into treatment response variability.

      Keywords

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