Characterization of central pain mechanisms using simultaneous spinal cord-brain functional imaging

使用同步脊髓-脑功能成像表征中枢疼痛机制

• 批准号: 10241962
• 负责人: Gary H Glover
• 金额: $ 58.28万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241962
• 关键词: Advanced Development; Affect; American; Biological Markers; Brain; Brain Stem; Brain imaging; Brain region; Cardiac; Cardiovascular system; Central Nervous System Diseases; Classification; Complex; Data; Degenerative Disorder; Emotional; Emotions; Fibromyalgia; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Human; Image; Individual; Interdisciplinary Study; Knowledge; Link; Maintenance; Mediating; Modeling; Motion; Neuraxis; Nociception; Opioid; Pain; Pain intensity; Pattern; Procedures; Public Health; Research; Rest; Scientific Advances and Accomplishments; Societies; Spinal; Spinal Cord; Spinal cord injury; Stimulus; Structure; System; Technology; Time; central pain; central sensitization; chronic pain; chronic painful condition; conditioned pain modulation; cost; dorsal horn; healthy volunteer; improved; innovation; innovative technologies; insight; magnetic field; magnetic resonance imaging biomarker; mechanical pressure; motor disorder; nervous system imaging; neuroimaging; pain processing; pressure; response; spinal cord imaging; symposium; systems research

Significance: Chronic pain affects approximately 100 million Americans, costs our society half a trillion dollars per year, and is challenging to treat effectively. Functional magnetic resonance imaging (fMRI) of the brain - and more recently the spinal cord - have advanced our knowledge of the central nervous system (CNS) correlates of pain processing in humans. Additionally, brain fMRI is demonstrating much promise as a potential pain biomarker. Convention has been to perform brain/brainstem and, only more recently, spinal cord imaging separately. But a link between the human brain and spinal cord remains conspicuously missing. To fully characterize abnormal CNS mechanisms of chronic pain and pain modulation, we need to understand the intricate interplay between these structures. Preliminary Data: We have demonstrated successful simultaneous spinal cord-brainstem-brain fMRI by overcoming the magnetic field shimming obstacles. We have also demonstrated the ability to image the CNS correlates of pain and pain modulation. We propose to use this innovative technology of simultaneous spinal cord-brain fMRI to more fully characterize CNS mechanisms of chronic pain and pain modulation, and also to develop improved corticospinal biomarkers of the chronic pain condition fibromyalgia (FM). Specific Aims: In Aim 1, we will enhance our innovative simultaneous spinal cord-brain imaging sequence to minimize the impact of cardiovascular-induced spinal cord motion. We will contrast the optimized sequence against our currently working sequence while characterizing the CNS mechanisms of thermal pain intensity encoding. In Aim 2, we will characterize central sensitization (using pressure pain, temporal summation (TS) of pain, and resting state functional connectivity) and in Aim 3, descending modulation of pain (using conditioned pain modulation (CPM) and emotion reappraisal (ER)). Our preliminary data demonstrates feasibility and early insights into these mechanisms. Finally, in Aim 4, we will use the complete CNS imaging of pain and its modulation within our established multivariate pattern analysis (MVPA) models to better inform mechanistic knowledge and classification procedures. Overall Impact: Successful completion of our aims will advance scientific knowledge of the complex interplay between the spinal cord and brain in chronic pain and pain modulation. Our results and technology will be used to investigate other fields of human CNS research (e.g. motor disorders, spinal cord injury, degenerative conditions, etc). Additionally, we will have advanced development of objective biomarkers of pain. Future directions of this research will apply these CNS biomarkers for neuroprognosis and neuroprediction to help reduce the public health crisis of pain.

意义：慢性疼痛影响约1亿美国人，使我们的社会损失半百万美元 每年，有效治疗具有挑战性。大脑的功能磁共振成像（fMRI） - 最近，脊髓 - 提高了我们对中枢神经系统（CNS）的了解 人类疼痛处理的相关性。此外，大脑fMRI表现出很大的希望是一种潜力 疼痛生物标志物。惯例是执行大脑/脑干，直到最近才是脊髓成像 分别地。但是人脑和脊髓之间的联系仍然显着缺失。完全 表征异常的CNS慢性疼痛和疼痛调节机制，我们需要了解 这些结构之间的复杂相互作用。 初步数据：通过 克服磁场的刺激性障碍物。我们还展示了成像中枢神经系统的能力 疼痛和疼痛调节的相关性。我们建议使用这种同时脊柱的创新技术 脐带脑fMRI更充分地表征了慢性疼痛和疼痛调节的中枢神经系统机制，也是 发展了慢性疼痛状况纤维肌痛（FM）的改善皮质脊髓生物标志物。 具体目的：在AIM 1中，我们将增强我们的创新性同时脊髓 - 脑成像序列 最小化心血管诱导的脊髓运动的影响。我们将对比优化的序列 在我们当前的工作序列上，同时表征了热疼痛强度的中枢神经系统机制 编码。在AIM 2中，我们将表征中心敏化（使用压力疼痛，时间求和（TS） 疼痛和静止状态功能连接）和AIM 3，疼痛的调节（使用条件 疼痛调节（CPM）和情绪重新评估（ER））。我们的初步数据证明了可行性和早期 洞悉这些机制。最后，在AIM 4中，我们将使用完整的CNS疼痛成像 我们已建立的多元模式分析（MVPA）模型中的调制，以更好地告知机理 知识和分类程序。 总体影响：成功完成我们的目标将促进对复杂相互作用的科学知识 在慢性疼痛和疼痛调节中的脊髓和大脑之间。我们的结果和技术将被使用 研究人类中枢神经系统研究的其他领域（例如运动障碍，脊髓损伤，退化性 条件等）。此外，我们还将对疼痛的客观生物标志物进行高级发展。未来 这项研究的方向将将这些CNS生物标志物应用于神经受损和神经误解以帮助 减少痛苦的公共卫生危机。