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: 10470381
• 负责人: ALEXANDRE DASILVA
• 金额: $ 72.04万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470381
• 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 pain management; chronic painful condition; clinical pain; cost; effective therapy; experience; fibromyalgia pain; fibromyalgia patients; interdisciplinary approach; network models; neural network; non-opioid analgesic; noninvasive brain stimulation; 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.

项目摘要 /摘要 美国的痛苦很普遍且昂贵，三分之一的人遭受了造成的痛苦 经济负担每年接近6000亿美元。这个问题是由于我们缺乏了解 大多数形式的慢性疼痛的基本机制又阻碍了我们发展新的能力 有效的治疗方法。纤维肌痛（FM）是一种常见的慢性疼痛状况，其病理在很大程度上是 未知。现有的研究表明，大脑在这些中可能在疼痛表达中起重要作用 个人。尽管未经测试，但兴奋性和抑制性脑活动的失衡可能导致不稳定 神经网络对外部刺激敏感，这可能导致FM疼痛。高度敏感和不稳定 已经在各种物理和生物系统以及此类网络中观察到网络 扰动会导致系统上活动的爆炸性和全球繁殖。一个基础 已经引入了高度敏感系统的机理，称为爆炸性同步（ES） 在过去的十年中，积极研究。 ES是一种现象，其中刺激强度的略有增加 应用于网络，可以通过全局网络同步导致状态过渡。我们在这里 假设ES可能是FM大脑超敏反应的潜在机制，并且有针对性的 与非侵入性大脑刺激的接近可能会减少某些条件或ES的状况或随后的疼痛 这些患者。我们的试验脑电图（EEG）数据显示，FM大脑显示网络 为ES准备的配置。临床疼痛更多的人增加了大脑中的ES状况 网络。此外，当这些患者经过实验后疼痛增加时 施加到拇指上的压力疼痛刺激，它们表现出ES的同时增加。了解如何 大脑内部超敏反应的发展可能导致慢性疼痛在医学领域未知 这是该提议的主要主题。我们认为，发现超敏反应的潜在机制 FM大脑可能会导致对中枢神经系统敏感的更基本的理解 在这种疼痛状态（以及其他其他疼痛状态），瞄准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，我们根据神经科学的跨学科方法提出了三个目标， 物理，医学和数学：AIM 1。证明与无疼痛相比，有FM的人 对照，显示EEG评估的ES的大脑特征。目标2。计算模型 超敏FM大脑的基本机制，并确定可能减少大脑的关键目标区域 高敏性。目标3。测试高清经颅直流电流刺激（HD-TDC）的能力 离散的网络区域以减少大脑内部的ES条件。