Neurobiological Phenotyping Core

神经生物学表型核心

• 批准号: 10765812
• 负责人: RICHARD E HARRIS
• 金额: $ 52.97万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10765812
• 关键词: Neurobiological; Phenotyping; Core

PROJECT SUMMARY / ABSTRACT NEUROBIOLOGICAL PHENOTYPING CORE The University of Michigan (UM) MRC Neurobiological Phenotyping Core (NPC) is composed of an experienced multidisciplinary team with expertise in the development and large-scale implementation of state-of-the-art methods to investigate the neurobiological mechanisms of chronic pain. These include functional magnetic resonance imaging (fMRI), quantitative sensory testing (QST), and measures of inflammation and autonomic nervous system function. In support of the UM MRC, these methods will be used in parallel to identify key neurobiological markers of chronic low back pain (cLBP) that can be used a priori to infer what treatments are likely to work in different patient endotypes – the ultimate goal of precision medicine and the BACPAC initiative. These analyses will help determine how multiple treatments uniquely affect pain mechanisms, a critical step for the development of new efficacious analgesics. The NPC is well suited to perform mechanistic studies in cLBP, as we have used our methods for nearly two decades in clinical and mechanistic studies to identify peripheral and central neurobiological characteristics in various chronic pain conditions, including cLBP. Because of the complexity of chronic pain, we believe that a comprehensive understanding of pain mechanisms in clinical populations is essential for improving pain management. This core, working in tandem with the Clinical and Behavioral Research Phenotyping and Informatics Cores, will primarily serve to facilitate Aim 3 of this proposed application by providing the technical expertise necessary to acquire and analyze neurobiological measures. The Specific Aims of the UM BACPAC MRC are: 1) Perform Interventional Response Phenotyping in cLBP patients (n=500). We will perform a pragmatic trial using in a cohort of cLBP patients, who will be randomized to receive a sequence of interventions known to be effective in cLBP including: mindfulness-based cognitive therapy, physical therapy and exercise, duloxetine, gabapentin, or self-acupressure; 2) Demonstrate that currently available, clinically-derived measures, can predict differential responsiveness to the above therapies. We will leverage the study in Aim 1 to identify predictors for commonly used cLBP therapies including: demographics, psychological assessment, clinical factors based on a structured physical examination, questionnaires assessing pain mechanisms, and structural imaging of the back and pelvis; 3) Perform deep phenotyping in a subset of the individuals in the Interventional Response Phenotyping Study described in Aim 1, to identify new experimental measures including: functional neuroimaging, QST, inflammation, and autonomic tone that predict differential responsiveness to our therapies, as well as to infer mechanisms of action of treatments (n=200). The NPC will focus on a subset of 200 individuals from the larger cohort in Aims 1 and 2, and perform expanded phenotyping studies that will occur prior to each 12-week treatment period and prior to receiving any interventional procedures; and 4) To provide data, research methods, and leadership to the broader BACPAC initiative.

项目概要/摘要 神经生物学表型核心 密歇根大学 (UM) MRC 神经生物学表型核心 (NPC) 由经验丰富的专家组成 多学科团队，拥有开发和大规模实施最先进技术的专业知识 研究慢性疼痛的神经生物学机制的方法包括功能磁。 磁共振成像 (fMRI)、定量感觉测试 (QST) 以及炎症和自主神经测量 为了支持 UM MRC，这些方法将并行使用来识别关键。 慢性腰痛 (cLBP) 的神经生物学标志物可用于先验地推断治疗方法 可能适用于不同的患者内型——精准医学和 BACPAC 倡议的最终目标。 这些分析将有助于确定多种治疗如何独特地影响疼痛机制，这是治疗疼痛的关键一步。 NPC 非常适合进行 cLBP 的机制研究， 因为我们在临床和机制研究中使用我们的方法近二十年来识别外周 以及各种慢性疼痛的中枢神经生物学特征，包括 cLBP。 慢性疼痛的复杂性，我们认为临床上全面了解疼痛机制 这一核心与临床和临床部门协同工作对于改善疼痛管理至关重要。 行为研究表型和信息学核心，将主要用于促进本提议的目标 3 通过提供获取和分析神经生物学测量所需的技术专业知识来应用。 UM BACPAC MRC 的具体目标是： 1) 对 cLBP 进行干预反应表型分析 我们将在一组 cLBP 患者中进行一项实用试验，这些患者将被随机分为 接受一系列已知对 cLBP 有效的干预措施，包括： 基于正念的认知 治疗、物理治疗和运动、度洛西汀、加巴喷丁或自我穴位按摩 2) 证明： 目前可用的临床衍生测量可以预测对上述疗法的不同反应。 我们将利用目标 1 中的研究来确定常用 cLBP 疗法的预测因素，包括： 人口统计、心理评估、基于结构化体检的临床因素、 评估疼痛机制以及背部和骨盆结构成像的调查问卷 3) 进行深度检查； 在 Aim 中描述的干预反应表型研究中对部分个体进行表型分析 1、确定新的实验措施，包括：功能神经影像、QST、炎症和自主神经 预测对我们治疗的不同反应的语气，以及推断作用机制 NPC 将重点关注目标 1 和 2 中较大群体中的 200 名个体。 并在每个 12 周治疗期之前和之前进行扩展表型研究 接受任何干预程序；以及 4) 向 更广泛的 BACPAC 倡议。