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.

项目摘要/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)由一位经验丰富的 具有开发和大规模实施最先进技术的专业知识的多学科团队 方法探讨慢性疼痛的神经生物学机制。其中包括功能磁性 磁共振成像(FMRI)、定量感觉测试(QST)以及炎症和自主神经的测量 神经系统功能。为了支持UM MRC，将并行使用这些方法来标识密钥 可先验推断治疗方法的慢性下腰痛(CLBP)的神经生物学标记物 可能适用于不同的患者内型--这是精准医学和BACPAC计划的终极目标。 这些分析将有助于确定多种治疗方法如何独特地影响疼痛机制，这是 新型高效止痛药的开发。全国人大非常适合在cLBP中进行力学研究， 因为我们已经使用我们的方法在临床和机制研究中识别外周血管 以及各种慢性疼痛情况下的中枢神经生物学特征，包括cLBP。因为 慢性疼痛的复杂性，我们相信在临床上全面了解疼痛的机制 人口是改善疼痛管理的关键。这一核心，与临床和 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进行应用。 UM bacpac MRC的具体目标是：1)在慢性下腰痛患者中进行介入反应表型分析 受试者500例。我们将在cLBP患者队列中进行一项务实的试验，这些患者将被随机分配到 接受一系列已知对慢性下腰痛有效的干预措施，包括：基于正念的认知 治疗、物理治疗和锻炼、度洛西汀、加巴喷丁或自我穴位按压；2)证明 目前可用的、临床衍生的方法可以预测对上述疗法的不同反应。 我们将利用目标1中的这项研究来确定常用cLBP疗法的预测因素，包括： 人口统计学，心理评估，基于结构化体检的临床因素， 评估疼痛机制的问卷，以及背部和骨盆的结构成像；3)进行深度检查 AIM中的干预反应表型研究中部分个体的表型分析 1、确定新的实验指标，包括：功能神经成像、QST、炎症和自主神经 预测对我们的治疗的不同反应的语气，以及推断 治疗(n=200)。全国人大将把重点放在目标1和目标2中较大队列中的200人子集上， 并在每个12周的治疗期之前和之前进行扩大的表型研究 接受任何干预程序；以及4)提供数据、研究方法和领导 更广泛的BACPAC倡议。