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，给我们的社会造成了5000亿美元的损失 每年，并且有效地治疗是具有挑战性的。大脑的功能性磁共振成像(FMRI)- 以及最近的脊髓--促进了我们对中枢神经系统(CNS)的了解 人类疼痛处理的关联性。此外，脑功能磁共振成像显示出很大的潜力。 疼痛生物标记物。传统的做法是进行脑/脑干成像，直到最近才开始进行脊髓成像 分开的。但人类大脑和脊髓之间的联系仍然明显缺失。充分地 刻画慢性疼痛的中枢神经系统异常机制和疼痛调制，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：我们已经成功地展示了脊髓-脑干-脑功能磁共振成像的成功 克服磁场摆动的障碍。我们还演示了成像CNS的能力 疼痛和疼痛调制的相关性。我们建议使用这项创新的同步脊柱技术 脊髓-脑功能磁共振成像，以更全面地表征慢性疼痛和疼痛调制的中枢机制，也 开发慢性疼痛条件下纤维肌痛(FM)的改进皮质脊髓生物标记物。 具体目标：在目标1中，我们将增强我们创新的同步脊髓-大脑成像序列，以 将心血管引起的脊髓运动的影响降至最低。我们将对比优化后的序列 与我们目前的工作顺序不同，同时描述了热痛强度的中枢神经系统机制 编码。在目标2中，我们将表征中枢敏感化(使用压痛、时间总和(TS) 疼痛和静息状态的功能连接)，以及在目标3中，对疼痛的下行调制(使用条件化 疼痛调制(CPM)和情绪再评估(ER))。我们的初步数据证明了可行性和及早 对这些机制的洞察。最后，在目标4中，我们将使用完整的中枢神经系统对疼痛及其 在我们已建立的多变量模式分析(MVPA)模型中进行调制，以更好地了解机制 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 脊髓和大脑之间的慢性疼痛和痛觉调制。我们的成果和技术将用于 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、退行性疾病 条件等)。此外，我们还将进一步开发疼痛的客观生物标记物。未来 本研究的方向将为应用这些中枢神经系统生物标志物进行神经预后和神经预测提供帮助 减轻公共卫生危机带来的痛苦。

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.