Boosting mind-body mechanisms and outcomes for chronic pain

摘要 虽然许多身心疗法已显示出对慢性疼痛的承诺，但任何单一形式的疗效 治疗通常是适度的，找到一种提高临床效果的方法是一个至关重要的目标。是 在最近的医学研究所（IOM）关于疼痛的报告中， 这种方法是最佳的疼痛管理。多模式镇痛策略被认为可以提高 同时针对导致慢性疼痛的多个途径。身心疗法 已经显示出治疗疼痛的希望，并且许多这样的疗法（例如，正念冥想（MM）训练） 实际上被描述为占主导地位的“头脑”，利用自上而下的大脑机制， 行动，而没有充分整合自下而上的“机构”机制。更好地利用“思想”和“身体” 通过多模式治疗方法的元素可以通过神经生理学增强临床结果， 中枢神经系统内的整合（即，脑）。本提案的总体目标是评估 以及在常见的慢性疼痛病症-偏头痛中发生这种整合。我们的三个项目将 目标3个关键的和相互关联的病理生理过程的特点偏头痛，以及如何 “自上而下”和“自下而上”的干预措施都能减轻这种病态。为了加强MM训练，我们提出了一个 特异性靶向、自下而上的治疗，也显示出治疗偏头痛的前景-经皮迷走神经 神经刺激（tVNS）。我们将使用最近开发的优化tVNS方法，该方法可以门控刺激， 呼吸节律（即，耳迷走神经传入神经刺激（RAVANS）， 在概念上和神经生理学上增强了tVNS与MM组合的潜在协同作用， 它自己的非判断性注意力集中在平静和警觉的呼吸上。这三个项目都将适用 基线时和联合治疗8周后的神经影像学和其他生理和行为工具 RAVANS或Sham tVNS与MM或教育对照。目标1，由项目1解决，将调查 脑干和皮质机制，用于降低皮质/皮质下兴奋过度。目标2，由 项目2，将评估MM+RAVANS tVNS在自主和中央自主网络中的改进 功能障碍目标3由项目3解决，将使用多模式PET/MR成像和最近开发的 用于评估MM+RAVANS tVNS疗法的抗神经炎症作用的神经胶质活化配体。目标4将 研究目标1至3中评估的神经生物学变化如何通过中介相互关联， 其他分析由神经影像学和生物统计学核心进行，而临床核心和 管理核心将支持我们的协同研究设计的招募和管理。

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.