Explosive Synchronization of Brain Network Activity in Chronic Pain

慢性疼痛中大脑网络活动的爆炸性同步

• 批准号: 10015206
• 负责人: ALEXANDRE DASILVA
• 金额: $ 74.59万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015206
• 关键词: Analgesics; Anesthesia procedures; Behavior; Brain; Brain region; Characteristics; Computer Models; Computers; Conscious; Data; Development; Economic Burden; Electroencephalogram; Epidemic; Epilepsy; Exhibits; Failure; Fibromyalgia; Goals; Human; Hypersensitivity; Individual; Lead; Mathematics; Medical; Medicine; Modeling; Motor Cortex; Neuraxis; Neurobiology; Neurosciences; Outcome; Pain; Pain-Free; Painless; Pathologic; Pathology; Patients; Persistent pain; Physics; Pilot Projects; Play; Population; Process; Property; Research; Rest; Role; Severities; Stimulus; System; Testing; Thumb structure; Time; United States; base; biological systems; chronic pain; chronic painful condition; clinical pain; cost; effective therapy; experience; fibromyalgia pain; fibromyalgia patients; interdisciplinary approach; network models; neural network; non-opioid analgesic; novel; novel strategies; opioid mortality; opioid overuse; pain reduction; pressure; prospective; sensory stimulus; treatment strategy

PROJECT SUMMARY / ABSTRACT Pain in the United States is common and costly, with over 1 in 3 individuals being afflicted causing an economic burden approaching $600 billion annually. This problem results from our lack of understanding the underlying mechanisms of most forms of chronic pain which in turn has hampered our ability to develop new effective treatments. Fibromyalgia (FM) is a common chronic pain condition whose pathology is largely unknown. Existing research suggests that the brain may play a significant role in pain expression in these individuals. Although untested, an imbalance in excitatory and inhibitory brain activity may lead to an unstable neural network sensitized to external stimuli and this may lead to pain in FM. Hypersensitive and unstable networks have been observed in various physical and biological systems, and in such networks, small perturbations can give rise to explosive and global propagation of activity over the system. One underlying mechanism of hypersensitive systems, called explosive synchronization (ES), has been introduced and actively studied over the past decade. ES is a phenomenon wherein small increases in stimulation strength applied to a network, can lead to an abrupt state transition through global network synchronization. Here we hypothesize that ES may be an underlying mechanism of the hypersensitivity of the FM brain, and a targeted approach with non-invasive brain stimulation may reduce conditions or ES and subsequent pain in some of these patients. Our pilot electroencephalogram (EEG) data showed that the FM brain displays network configurations primed for ES. Individuals with more clinical pain had increased ES conditions within their brain networks. Furthermore, when these same patients experienced an increase in pain following an experimental pressure pain stimulus applied to the thumb, they exhibited a concomitant increase in ES. Understanding how the development of hypersensitivity within the brain can lead to chronic pain is an unknown in the medical field and is the major theme of this proposal. We posit that finding the underlying mechanism of hypersensitivity in the FM brain could lead to a more fundamental understanding of the central nervous system sensitization seen in this pain state (and potentially others), and targeting this phenomenon might be an effective new treatment strategy. To achieve this goal, we propose three aims based on interdisciplinary approaches of neuroscience, physics, medicine, and mathematics: Aim 1. Demonstrate that individuals with FM, as compared to pain free controls, display brain characteristics of ES as assessed with EEG. Aim 2. Computationally model the underlying mechanism(s) of the hypersensitive FM brain and identify key target regions that might reduce brain hypersensitivity. Aim 3. Test the ability of high definition transcranial direct current stimulation (HD-tDCS) at discrete network regions to reduce conditions of ES within the brain.

项目概要/摘要 在美国，疼痛很常见且代价高昂，超过三分之一的人遭受痛苦，导致 每年的经济负担接近6000亿美元。这个问题是由于我们不了解 大多数慢性疼痛的潜在机制，反过来又阻碍了我们开发新疼痛的能力 有效的治疗。纤维肌痛 (FM) 是一种常见的慢性疼痛疾病，其病理学很大程度上取决于 未知。现有研究表明，大脑可能在这些患者的疼痛表达中发挥重要作用。 个人。尽管未经测试，兴奋性和抑制性大脑活动的不平衡可能会导致不稳定 神经网络对外部刺激敏感，这可能会导致 FM 疼痛。过敏且不稳定 网络已在各种物理和生物系统中被观察到，并且在这些网络中，小型网络 扰动可能会导致系统上的活动发生爆炸性的全球传播。一项标的 超敏感系统的机制，称为爆炸性同步（ES），已经被引入并 过去十年积极研究。 ES是一种刺激强度小幅增加的现象 应用于网络时，可以通过全局网络同步导致突然的状态转换。在这里我们 假设 ES 可能是 FM 大脑超敏反应的潜在机制，并且有针对性 非侵入性脑刺激方法可能会减轻某些疾病或 ES 以及随后的疼痛 这些病人。我们的试点脑电图 (EEG) 数据显示 FM 大脑显示网络 为 ES 准备的配置。临床疼痛较多的个体大脑内 ES 状况增加 网络。此外，当这些相同的患者在实验后经历疼痛增加时 当对拇指施加压痛刺激时，他们表现出 ES 随之增加。了解如何 大脑内过度敏感的发展会导致慢性疼痛，这在医学领域是未知的 是本提案的主题。我们认为，找到超敏反应的潜在机制 FM大脑可以使我们对中枢神经系统敏化有更基本的了解 在这种疼痛状态（以及可能的其他状态）中，针对这种现象可能是一种有效的新疗法 战略。为了实现这一目标，我们基于神经科学的跨学科方法提出了三个目标， 物理、医学和数学：目标 1. 证明 FM 患者与无痛患者相比 对照，显示通过 EEG 评估的 ES 的大脑特征。目标 2. 计算模型 超敏感 FM 大脑的潜在机制，并确定可能降低大脑功能的关键目标区域 超敏反应。目标 3. 测试高清经颅直流电刺激 (HD-tDCS) 的能力 离散网络区域，以减少大脑内 ES 的状况。