Boosting mind-body mechanisms and outcomes for chronic pain

促进慢性疼痛的身心机制和结果

基本信息

批准号：
10000024
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
项目类别：
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/10000024
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 mindfulness meditation multi-component intervention multimodality network dysfunction neuroimaging neuroinflammation neurophysiology recruit respiratory response stem synergism tool trial design vagus nerve stimulation

项目摘要

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.

抽象的虽然许多身心疗法已显示出治疗慢性疼痛的希望，但任何单一疗法的功效治疗通常是温和的，找到一种提高临床结果的方法是一个至关重要的目标。医学研究所 (IOM) 最近的疼痛报告中有详细记录并推荐了多模式治疗多模式镇痛策略被认为是最佳的疼痛管理方法。通过同时针对导致慢性疼痛的多种途径来治疗患者。已显示出治疗疼痛的希望，并且许多此类疗法（例如正念冥想（MM）训练）实际上主要被描述为“思想”，利用自上而下的基于大脑的机制行动，而没有充分整合基于“身体”的自下而上的机制更多地使用“思想”和“身体”。多模式治疗方法的要素可以通过神经生理学增强临床结果我们在该提案中的总体目标是评估如何在中枢神经系统（即大脑）内进行整合。我们的 3 个项目将针对常见的慢性疼痛疾病——偏头痛进行这种整合。目标 3 个关键且相互关联的偏头痛特征的病理生理过程，以及如何 “自上而下”和“自下而上”的干预措施都可以缓解这种病态，为了增强 MM 培训，我们提出了一种方法。有针对性的自下而上疗法也显示出治疗偏头痛的希望 - 经皮迷走神经我们将使用最近开发的优化 tVNS 方法来控制刺激。呼吸节律（即呼吸门控耳传入神经刺激，RAVANS），增强了 tVNS 与 MM 相结合的概念上和神经生理学上的潜在协同作用它自己的非评判性注意力集中在平静和警觉的呼吸上，这三个项目都适用。基线和 8 周组合后的神经影像学和其他生理和行为工具 RAVANS 或 Sham tVNS 与 MM 或教育控制的目标 1（由项目 1 解决）将进行调查。减少皮质/皮质下过度兴奋的脑干和皮质机制，解决方法：项目2，将评估MM+RAVANS tVNS在自主和中央自主网络方面的改进项目 3 所解决的目标 3 将使用多模态 PET/MR 成像和最近开发的一种技术。神经胶质细胞活化配体以评估 MM+RAVANS tVNS 疗法的抗神经炎症作用，目标 4。研究目标 1 至 3 中评估的神经生物学变化如何通过中介和神经影像和生物统计核心进行的其他分析，而临床核心和管理核心将支持我们协同研究设计的招募和管理。