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: 10653975
• 负责人: ALEXANDRE DASILVA
• 金额: $ 69.05万
• 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/10653975
• 关键词: Analgesics; Anesthesia procedures; Behavior; Brain; Brain region; Central Nervous System; Characteristics; Computer Models; Computers; Conscious; Data; Development; Economic Burden; Electroencephalography; Electronics; Epidemic; Epilepsy; Exhibits; Failure; Fibromyalgia; Goals; Human; Hypersensitivity; Individual; Mathematics; Medical; Medicine; Modeling; Motor Cortex; 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; 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; novel therapeutic intervention; opioid mortality; opioid overuse; pain reduction; pressure; prospective; sensory stimulus; transcranial direct current stimulation; 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