Boosting mind-body mechanisms and outcomes for chronic pain

摘要 虽然许多心身疗法已经显示出对慢性疼痛的希望，但任何单一疗法的疗效 治疗通常是温和的，找到一种方法来提高临床结果是一个至关重要的目标。它是 有很好的记录，并在最近的医学研究所(IOM)关于疼痛的报告中建议，多模式 该方法是疼痛控制的最佳方法。多模式止痛策略被认为增加了对 通过同时靶向导致慢性疼痛的多条路径来治疗患者。心身疗法 已经显示出对疼痛的希望，许多这样的疗法(例如，正念冥想(MM)训练)是 实际上被描述为主要是“头脑”，利用自上而下的基于大脑的机制 行动，而不是完全整合自下而上的基于“身体”的机制。更多地使用“精神”和“身体” 通过多模式治疗方法的元素可能通过神经生理学来改善临床结果 中枢神经系统(即大脑)内的整合。我们在这份提案中的总体目标是评估如何 而这种整合发生在一种常见的慢性疼痛障碍-偏头痛的地方。我们的3个项目将 目标3偏头痛的关键和相互关联的病理生理过程，以及如何 “自上而下”和“自下而上”的干预措施都缓解了这种病态。为了加强MM培训，我们提出了一个 有针对性的、自下而上的疗法也显示出对偏头痛--经皮迷走神经的治疗前景 神经刺激(TVNS)。我们将使用最近开发的一种优化的tVNS方法来实现刺激 呼吸节律(即呼吸门控耳迷走传入神经刺激，RAVANS)， 在概念上和神经生理学上增强TVNS与MM的潜在协同作用， 它本身的重点是以冷静和警觉的心态呼吸，而不是评判。所有这三个项目都将适用 基线和联合治疗8周后的神经成像和其他生理和行为工具 RAVAN或Sham TVNS与MM或教育控制。目标1，由项目1解决，将调查 降低皮质/皮质下过度兴奋性的脑干和皮质机制。目标2，发信人 项目2，将评估MM+RAVANS在自主和中央自主网络中的tVNS改进 功能障碍。由项目3解决的目标3将使用多模式PET/MR成像和最近开发的 用于评估MM+RAVANS TVNS治疗的抗神经炎效应的神经胶质激活配体。目标4将 调查目标1至3中评估的神经生物学变化如何通过调解和 由神经成像和生物统计核心执行的其他分析，而临床核心和 管理核心将支持我们协同研究设计的招聘和管理。

Abstract While many mind-body therapies have shown promise for chronic pain, the efficacy of any single-modality treatment is typically modest, and finding a way to boost clinical outcomes is a crucially important goal. It is well documented, and recommended in the recent Institute of Medicine (IOM) report on pain, that a multimodal approach is optimal for pain management. Multimodal analgesic strategies are thought to enhance benefits to patients by simultaneously targeting multiple pathways that contribute to chronic pain. Mind-body therapies have shown promise for pain, and many such therapies (e.g., mindfulness meditation (MM) training) are actually characterized as predominantly “mind,” taking advantage of top-down brain-based mechanisms of action, without fully integrating bottom-up “body”-based mechanisms. A greater use of “mind” and “body” elements via a multimodal therapeutic approach may enhance clinical outcomes through neurophysiological integration within the central nervous system (i.e., brain). Our overall goal in this proposal is to evaluate how and where such integration takes place for a common chronic pain disorder - migraine. Our 3 Projects will target 3 critical and inter-related pathophysiological processes that characterize migraine headache, and how both “top-down” and “bottom-up” interventions mitigate this pathology. To augment MM training, we propose a specifically-targeted, bottom-up therapy that has also shown promise for migraine - transcutaneous vagus nerve stimulation (tVNS). We will use a recently developed optimized tVNS approach that gates stimulation to the respiratory rhythm (i.e., respiratory-gated auricular vagal afferent nerve stimulation, RAVANS), which enhances the potential synergy, both conceptually and neurophysiologically, of combining tVNS with MM, with its own focus of non-judgmental attention on breathing with a calm and alert mind. All three projects will apply neuroimaging and other physiological and behavioral tools at baseline and following 8-weeks of a combination of RAVANS or Sham tVNS with MM or education control. Aim 1, addressed by Project 1, will investigate brainstem and cortical mechanisms for reducing cortical/subcortical hyperexcitability. Aim 2, addressed by Project 2, will evaluate MM+RAVANS tVNS improvements in autonomic and central autonomic network dysfunction. Aim 3, addressed by Project 3, will use multimodal PET/MR imaging and a recently developed ligand for glial activation to assess anti-neuroinflammatory effects of MM+RAVANS tVNS therapy. Aim 4 will investigate how the neurobiological changes assessed in Aims 1 to 3 are inter-related through mediation and other analyses performed by the Neuroimaging and Biostatistical Core, while the Clinical Core and Administrative Core will support recruitment and administration of our synergistic study design.