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.

项目摘要 慢性疼痛对个人和社会来说是高度普遍的，而且昂贵。一旦慢性，疼痛就很难治疗 或反向预防和早期治疗以改善长期结局的早期识别密钥。 来自我们实验室以及其他人的最新脑成像数据提供了结构特性的证据 边缘大脑的体积和/或形状，例如伏隔核（NAC），杏仁核和海马 可以预测下急性下腰痛（SBP）后，低背痛的可能性是“编年期”的可能性 （持续时间为6-12周）。边缘大脑在预测对慢性疼痛的脆弱性或韧性中的作用与 人们普遍认为，慢性疼痛部分是由于外周伤害感受器之间的相互作用 和脆弱的边缘大脑圈子，众所周知会介导负面的情感和厌恶性学习 与慢性疼痛有关。因此，了解边缘脑电路的结构特性如何 预测人类慢性疼痛的风险或韧性具有创新性，并且具有很高的翻译意义。 但是，对慢性疼痛过渡的大脑成像研究的数量仍然非常有限， 范围，因此，我们仍然对确切的边缘电路和结构连通性的了解仍然很差 对慢性疼痛的潜在风险或适应力。迄今为止，只有一项小型研究报告了当地的白质 特性可以预测对疼痛回归的弹性。此外，没有大脑成像研究 研究了重要的生物学变量（例如性别或已建立的临床表型）（例如存在）的作用 或缺乏下背痛的神经性成分。因此，该提议的总体目的是 使用艺术结构映射技术来研究局部解剖特性（例如，体积，形状， 神经突导向）和白质连接性，以识别生物标志物的疼痛编年期。我们将使用2 不同的方法，一种基于生物学上合理的假设，一种基于数据驱动的假设的方法 在我们的初步数据中确定。此外，该提案将探讨性别和临床低背部的影响 这些生物标志物上的疼痛表型。我们将招募SBP患者并获得大脑解剖和多壳 基线和6个月的随访时扩散加权成像数据。患者将被归类为康复 或后续访问后持久。 AIM 1将测试基线本地和全球灰色，白质差异 在边缘大脑区域的恢复和持续患者之间，例如NAC，杏仁核，海马，海马， 前扣带回皮层和白质途径以其在慢性疼痛中的作用而闻名（例如，扣带 束和内部胶囊）和评估这些措施是否在随访时发生变化。 AIM 2将使用数据 - 通过驱动的方法来检查全球和局部灰色，白质特性，可预测慢性的风险或韧性 疼痛。最后，AIM 3将探讨性别，存在或不存在根本性症状的影响 在目标1和2中确定的生物标志物。