Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats

Katherine Byrd, Makayla Lund, Yan Pan, Brandon H. Chung, Kaitlyn Child, Danny Fowler, Jared Burns-Martin, Mythili Sanikommu, Hallie Henderson, Caroline Gregory, Regina K. Fleming, Jennifer Yanhua Xie
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Abstract

Migraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action.Female rats were subjected to a “two-hit” approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining.Following Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation.These findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.
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整骨疗法缓解雌性大鼠偏头痛样疼痛的潜在机制
偏头痛是美国致残的主要原因,而使用非药物治疗方法,如整骨疗法(OMT)已显示出良好的前景。尽管这种疗法具有潜力,但由于缺乏对其机理的了解,因此阻碍了它的广泛应用。本研究旨在探讨整骨疗法治疗急性偏头痛的疗效,并揭示其潜在的作用机制。雌性大鼠接受了 "两击 "方法诱发偏头痛样疼痛,包括向斜方肌双侧注射完全弗氏佐剂(CFA)(第一击),然后在注射完全弗氏佐剂后第 6 天接触人类偏头痛诱因茵贝酮(第二击)。软组织和关节技术应用于颈椎区域的急性缓解或反复预防治疗。通过行为测试和免疫组化染色评估了皮肤异感症和三叉神经系统激活情况。吸入茵贝酮后,CFA诱发的大鼠表现出眶周和后爪异感。吸入翁贝酮后立即使用 OMT 作为终止治疗可部分缓解皮肤异感。作为预防性措施,使用三次 OMT 可完全抑制触觉过敏。这些研究结果从机理上揭示了OMT缓解偏头痛的潜力,并强调了其作为一种非药物治疗偏头痛途径的可行性。
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