Boosting mind-body mechanisms and outcomes for chronic pain

促进慢性疼痛的身心机制和结果

• 批准号: 10456004
• 负责人: VITALY NAPADOW
• 金额: $ 218.18万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456004
• 关键词: Address; Analgesics; Astrocytes; Attention; Autonomic Dysfunction; Base of the Brain; Behavioral; Biostatistics Core; Brain; Brain Stem; Breathing; Chronic; Chronic disabling pain; Clinical; Clinical Trials Design; Combined Modality Therapy; Complex; Data; Disease; Dysautonomias; Education; Elements; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Heart; Institute of Medicine (U.S.); Intervention; Ligands; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mediating; Mediation; Medical; Meditation; Microglia; Migraine; Mind; Mind-Body Intervention; Modality; Modeling; Neuraxis; Neurobiology; Outcome; Pain; Pain management; Pathology; Pathway interactions; Patients; Peripheral; Physiological; Positron-Emission Tomography; Process; Randomized; Reporting; Research; Research Design; Sensory; Techniques; Testing; Therapeutic; Training; Trigeminal System; Up-Regulation; afferent nerve; base; body-mind; central sensitization; chronic pain; chronic painful condition; glial activation; improved outcome; migraine treatment; mindfulness meditation; multi-component intervention; multimodality; network dysfunction; neuroimaging; neuroinflammation; neurophysiology; recruit; respiratory; response; stem; synergism; tool; trial design; vagus nerve stimulation

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.

抽象的 虽然许多思维体疗法对慢性疼痛表现出希望，但任何单模式的效率 治疗通常是适中的，找到一种提高临床结果的方法是至关重要的目标。这是 有据可查，并在最近的医学研究所（IOM）报告中推荐了多模式 方法最适合疼痛管理。据认为，多模式镇痛策略可以提高利益 通过简单地靶向多种导致慢性疼痛的途径来进行患者。思维体疗法 已经表现出对疼痛的希望，许多此类疗法（例如正念冥想（MM）训练）是 实际上以“思维”为主，利用了自上而下的基于大脑的机制 动作，没有完全整合自下而上的基于“身体”的机制。更多地使用“思维”和“身体” 通过多模式疗法方法的元素可以通过神经生理增强临床结果 中枢神经系统（即大脑）内的整合。我们在此提案中的总体目标是评估 发生这种整合的地方发生了常见的慢性疼痛障碍 - 偏头痛。我们的3个项目将 目标3特征偏头痛标头的关键和相关的病理生理过程，以及如何 “自上而下”和“自下而上”干预措施减轻了这种病理。要增强MM培训，我们建议 特定针对性的自下而上的疗法也显示出对偏头痛的有望 神经刺激（TVN）。我们将使用最近开发的优化电视方法，以刺激大门刺激 呼吸节奏（即，呼吸门控的耳走神经传入神经刺激，Ravans），ravans） 在概念和神经生理上都可以增强电视与MM的潜在协同作用， 它以平静而机敏的头脑将非判断性关注的重点放在呼吸上。这三个项目将适用 在基线时以及结合了8周之后的神经影像和其他身体和行为工具 具有MM或教育控制的Ravans或Sham TVN。 AIM 1，由项目1解决，将调查 脑干和皮质机制，用于降低皮质/皮层下过度刺激性。 AIM 2，解决 项目2，将评估MM+Ravans TVNS自主和中央自主网络的改进 功能障碍。 AIM 3，由项目3解决，将使用多模式宠物/MR成像，并最近开发 用于评估MM+Ravans TVNS治疗的抗神经炎症作用的胶质激活配体。目标4意志 研究目标1至3中评估的神经生物学变化如何通过调解和 神经影像和生物统计核心进行的其他分析，而临床核心和 行政核心将支持我们协同研究设计的招聘和管理。