Brain Structural Biomarkers of Risk and Resilience to Pain Chronification

疼痛风险和恢复能力的脑结构生物标志物

• 批准号: 10584169
• 负责人: Paul Geha
• 金额: $ 47.27万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584169
• 关键词: Acute; Address; Amygdaloid structure; Anatomy; Anisotropy; Anterior; Area; Back Pain; Biological; Biological Markers; Brain; Brain imaging; Chronic; Chronic low back pain; Classification; Clinical; Data; Deep Brain Stimulation; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Early identification; Early treatment; Emotional; External Capsule; Female; Globus Pallidus; Healthcare Systems; Hippocampus; Human; Individual; Internal Capsule; Knowledge; Learning; Light; Limbic System; Low Back Pain; Maps; Measures; Mediating; Neurites; Neuropathy; Nociception; Nucleus Accumbens; Numeric Rating Scale; Outcome; Pain; Pain Free; Pathway interactions; Patients; Peripheral; Phenotype; Prevention; Preventive treatment; Procedures; Prognostic Marker; Property; Radiculopathy; Reporting; Resolution; Risk; Risk Marker; Role; Scanning; Sciatica; Shapes; Societies; Structure; Symptoms; Techniques; Testing; Time; Ventral Striatum; Visit; biomarker identification; brain circuitry; chronic pain; cingulate cortex; clinical phenotype; cost; design; economic cost; follow-up; gray matter; high risk population; imaging study; improved; innovation; male; negative affect; novel; pain chronification; pain patient; painful neuropathy; pre-clinical; predict clinical outcome; prevent; recruit; resilience; risk prediction; sex; translational potential; water flow; white matter

PROJECT SUMMARY Chronic pain is highly prevalent and costly to individuals and society. Once chronic, pain is very hard to treat or reverse making early identification key for prevention and early treatment to improve long-term outcomes. Recent brain imaging data from our lab as well as others have provided evidence that the structural properties of the limbic brain, such as the volume and/or shape of nucleus accumbens (NAc), amygdala, and hippocampus can predict the likelihood of “chronification” of low-back pain after an episode of sub-acute low back pain (SBP) (duration 6-12 weeks). The role of the limbic brain in predicting vulnerability or resilience to chronic pain fits with the general understanding that chronic pain is partly due to an interaction between peripheral nociceptive input and vulnerable limbic brain circuitries, which are known to mediate the negative affective and aversive learning associated with chronic pain. Hence, understanding how the structural properties of the limbic brain circuitries predict risk or resilience to chronic pain in humans is innovative and has high translational significance. However, the brain imaging studies of the transition to chronic pain remain very limited in number and scope and, hence, we still have a poor understanding of the exact limbic circuitry and structural connectivity underlying risk of or resilience to chronic pain. To date, only one small study reported that local white matter properties can predict resilience to pain chronification. Furthermore, no brain imaging study of pain chronification investigated the role of important biological variables like sex or established clinical phenotypes like the presence or absence of a neuropathic component of the low back pain. Therefore, the overarching aim of this proposal is to use state of the art structural mapping techniques to study local anatomical properties (e.g. volume, shape, neurite orientation) and white matter connectivity to identify biomarkers for pain chronification. We will use 2 different approaches, one based on biologically plausible hypotheses, and one based on data driven hypotheses identified in our preliminary data. In addition, the proposal will explore the effect of sex and clinical low-back pain phenotypes on theses biomarkers. We will recruit SBP patients and obtain brain anatomical and multi-shell diffusion weighted imaging data at baseline and at 6 months follow-up. Patients will be classified as recovered or persistent after the follow-up visit. Aim 1 will test baseline local and global gray, white matter differences between recovered and persistent patients in areas of the limbic brains like NAc, amygdala, hippocampus, anterior cingulate cortex, and white matter pathways known for their role in chronic pain (e.g., the cingulum bundle and internal capsule) and assess whether these measures change at follow-up. Aim 2 will use a data- driven approach to examine global and local gray, white matter properties predicting risk or resilience to chronic pain. Finally, aim 3 will explore the effect of sex and presence or absence of radiculopathy symptoms on the biomarkers identified in Aims 1 and 2.

项目总结 慢性疼痛非常普遍，对个人和社会来说代价高昂。一旦是慢性的，疼痛就很难治疗了 或者逆转使早期识别成为预防和早期治疗的关键，以改善长期结果。 我们实验室和其他实验室最近的脑成像数据提供了证据表明， 边缘脑，如伏隔核(NAC)、杏仁核和海马体的体积和/或形状 可以预测亚急性腰痛(SBP)发作后腰痛“慢性化”的可能性 (持续6-12周)。边缘脑在预测慢性疼痛的脆弱性或恢复力方面的作用符合 普遍认为慢性疼痛的部分原因是外周伤害性输入之间的相互作用 和脆弱的边缘脑回路，它们被认为是负向情感和厌恶学习的中介。 与慢性疼痛有关。因此，了解边缘脑回路的结构特性 预测人类慢性疼痛的风险或弹性是创新的，具有很高的翻译意义。 然而，过渡到慢性疼痛的脑成像研究仍然非常有限，而且 因此，我们对边缘电路和结构连通性的确切理解仍然很差。 慢性疼痛的潜在风险或恢复力。到目前为止，只有一项小型研究报告称，局部脑白质 特性可以预测对疼痛时代化的弹性。此外，没有关于疼痛时代化的脑成像研究 调查了重要的生物变量如性别或已确定的临床表型如存在的作用 或缺少下腰痛的神经病变成分。因此，这项提案的总体目标是 使用最先进的结构映射技术来研究局部解剖属性(例如，体积，形状， 轴突方向)和白质连接，以确定疼痛时代化的生物标记物。我们将使用2 不同的方法，一种基于生物学上可信的假设，另一种基于数据驱动的假设 在我们的初步数据中确定了。此外，该提案还将探讨性别和临床腰背的影响 这些生物标记物上的疼痛表型。我们将招募SBP患者，并获得脑部解剖和多壳 基线和6个月随访时的弥散加权成像数据。患者将被归类为康复患者 或在后续访问后坚持。目标1将测试基线局部和全局灰质、白质差异 在恢复的和顽固的患者之间的边缘脑区域，如NAC，杏仁核，海马体， 前扣带回皮质和白质通路，以其在慢性疼痛中的作用而闻名(例如，扣带 束和内囊)，并评估这些措施在随访时是否发生变化。AIM 2将使用一个数据- 检查全球和局部灰质、白质特性预测慢性病风险或恢复能力的驱动型方法 疼痛。最后，目标3将探索性别和是否有神经根病症状对 目标1和目标2中确定的生物标志物。