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.

项目总结/摘要 在美国，疼痛是常见且昂贵的，超过三分之一的人受到折磨， 经济负担每年接近6000亿美元。这个问题是由于我们缺乏对 大多数形式的慢性疼痛的潜在机制，这反过来又阻碍了我们开发新的 有效的治疗。纤维肌痛（FM）是一种常见的慢性疼痛状况，其病理主要是 未知现有的研究表明，大脑可能在这些疼痛表达中发挥重要作用。 个体虽然未经测试，兴奋性和抑制性大脑活动的不平衡可能导致不稳定的 神经网络对外部刺激敏感，这可能导致FM疼痛。过敏和不稳定 网络已经在各种物理和生物系统中观察到，在这样的网络中， 扰动可引起活动在系统上的爆炸性和全球性传播。一个底层 介绍了超敏感系统的一种机制--爆炸同步， 在过去的十年里积极研究。ES是一种现象，其中刺激强度的小幅增加 应用于网络，可以通过全局网络同步导致突然的状态转换。这里我们 假设ES可能是FM大脑超敏反应的潜在机制，并且靶向的 非侵入性脑刺激方法可能会减少某些患者的病情或ES和随后的疼痛 这些病人。我们的飞行员脑电图（EEG）数据显示，FM大脑显示网络 为ES准备的配置。具有更多临床疼痛的个体在他们的大脑中具有增加的ES条件 网络.此外，当这些相同的患者在实验性疼痛后经历疼痛增加时， 当压力疼痛刺激施加到拇指时，它们表现出ES的伴随增加。了解如何 脑内超敏反应的发展可导致慢性疼痛 也是这个提案的主题。我们认为，发现过敏的潜在机制， FM大脑可以导致对中枢神经系统敏化的更基本的理解， 在这种疼痛状态（以及其他潜在的疼痛状态）中，针对这种现象可能是一种有效的新治疗方法。 战略为了实现这一目标，我们提出了三个目标，基于神经科学的跨学科方法， 物理、医学和数学：目标1。证明患有FM的人与无疼痛的人相比 对照组显示用EEG评估的ES的脑特征。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， 离散的网络区域，以减少脑内ES的条件。