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

意义：慢性疼痛影响着大约1亿美国人，使我们的社会损失了5万亿美元 每年，并且具有有效治疗的挑战性。脑功能磁共振成像（fMRI）- 以及最近的脊髓-已经推进了我们对中枢神经系统（CNS）的认识 人类疼痛处理的相关性。此外，大脑功能磁共振成像显示出很大的潜力， 疼痛生物标志物。传统的做法是进行脑/脑干成像，最近才进行脊髓成像 分开但是人类大脑和脊髓之间的联系仍然明显缺失。充分 描述慢性疼痛和疼痛调制的异常CNS机制，我们需要了解 这些结构之间错综复杂的相互作用。 初步数据：我们已经成功地证明了同步脊髓-脑干-脑功能磁共振成像， 克服磁场匀场障碍。我们还证明了对中枢神经系统成像的能力 疼痛和疼痛调节的相关性。我们建议使用这种创新的技术， 索脑功能磁共振成像，以更充分地表征慢性疼痛和疼痛调制的中枢神经系统机制， 开发慢性疼痛病症纤维肌痛（FM）的改进的皮质脊髓生物标志物。 具体目标：在目标1中，我们将增强我们创新的同步脊髓-脑成像序列， 最小化心血管引起的脊髓运动的影响。我们将对比优化后的序列 对照我们目前的工作序列，同时表征热痛强度的CNS机制， 编码.在目标2中，我们将表征中枢致敏（使用压迫性疼痛， 疼痛和静息状态功能连接），以及目标3中的疼痛下行调制（使用条件反射 疼痛调节（CPM）和情绪重新评价（ER））。我们的初步数据表明， 深入了解这些机制。最后，在目标4中，我们将使用疼痛的完整CNS成像及其 在我们建立的多变量模式分析（MVPA）模型中进行调制，以更好地告知机制 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认识 在慢性疼痛和疼痛调节中脊髓和大脑之间的联系。我们的成果和技术将被用于 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、退行性 条件等）。此外，我们将进一步开发疼痛的客观生物标志物。未来 这项研究的方向将应用这些CNS生物标志物进行神经预后和神经预测， 减少疼痛的公共卫生危机。

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.