Neurobiological Phenotyping Core

神经生物学表型核心

• 批准号: 9898109
• 负责人: RICHARD E HARRIS
• 金额: $ 221.9万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898109
• 关键词: Acupressure; Advocate; Affect; Analgesics; Autonomic nervous system; Back; Behavioral; Behavioral Research; Caring; Characteristics; Chronic; Chronic low back pain; Clinical; Clinical Research; Data; Degenerative polyarthritis; Development; Diabetic Neuropathies; Disease; Economic Factors; Enrollment; Facet joint structure; Fibromyalgia; Focus Groups; Functional Magnetic Resonance Imaging; Goals; Image; Individual; Inflammation; Informatics; Injections; Interstitial Cystitis; Intervention; Leadership; Light; Malignant Neoplasms; Measures; Methods; Michigan; Nervous System Physiology; Neurobiology; Online Systems; Operative Surgical Procedures; Pain; Pain management; Participant; Patient Outcomes Assessments; Patients; Pelvis; Peripheral; Phenotype; Physical Examination; Physical therapy exercises; Placebo Effect; Population; Procedures; Questionnaires; Randomized; Research; Research Methodology; Rheumatism; Rheumatoid Arthritis; Self Administration; Sensory; Sickle Cell Anemia; Spinal; Spine surgery; Steroids; Structure; Surveys; Systems Biology; Technical Expertise; Temporomandibular Joint Disorders; Testing; Translational Research; Universities; Vulvodynia; Work; actigraphy; base; chronic pain; chronic painful condition; cohort; demographics; duloxetine; experience; gabapentin; improved; individualized medicine; mindfulness based cognitive therapy; mindfulness-based stress reduction; multidisciplinary; neurobiological mechanism; neuroimaging; non-opioid analgesic; pain patient; pragmatic trial; precision medicine; predicting response; psychologic; racial and ethnic; randomized trial; response; self-management program; social; treatment duration; working group

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）由经验组成 多学科团队在开发和大规模实施中具有专业知识 研究慢性疼痛的神经生物学机制的方法。这些包括功能磁 共振成像（fMRI），定量感觉测试（QST）以及注射和自主神经的度量 神经系统功能。为了支持UM MRC，这些方法将并行使用以识别密钥 可以使用先验的慢性腰痛（CLBP）的神经生物学标记来推断哪些治疗方法是 可能在不同的患者内型中工作 - 精密医学和BACPAC倡议的最终目标。 这些分析将有助于确定多种治疗如何唯一影响疼痛机制，这是一个关键的步骤 开发新的有效镇痛药。 NPC非常适合在CLBP中进行机械研究 由于我们在临床和机械研究中使用了将近二十年的方法，以识别外围 以及包括CLBP在内的各种慢性疼痛条件下的中央神经生物学特征。因为 慢性疼痛的复杂性，我们认为对临床中疼痛机制有全面的了解 人群对于改善疼痛管理至关重要。这个核心与临床和 行为研究表型和信息核心将主要用来促进本提案的目标3 通过提供获得和分析神经生物学测量所需的技术专长来应用。 UM BACPAC MRC的具体目的是：1）在CLBP中进行介入的反应表型 患者（n = 500）。我们将在CLBP患者队列中进行一项务实的试验，他们将随机分配给 接受一系列已知在CLBP中有效的干预措施，包括：基于正念的认知 治疗，物理疗法和运动，杜洛西汀，加巴喷丁或自任服； 2）证明这一点 当前可用的临床措施可以预测对上述疗法的差异反应。 我们将在AIM 1中利用这项研究来确定常用CLBP疗法的预测因子，包括： 人口统计学，心理评估，基于结构化体格检查的临床因素， 评估疼痛机制以及背部和骨盆的结构成像的问卷； 3）执行深度 在AIM中描述的介入反应表型研究中，个体中的表型 1，确定新的实验措施，包括：功能性神经成像，QST，注射和自主神经 预测对我们疗法的差异反应的音调，并推断出作用机制 治疗（n = 200）。 NPC将重点关注来自AIMS 1和2中较大队列的200个人的子集， 并进行扩展的表型研究，该研究将在每个12周治疗期之前和之前进行 接受任何介入程序； 4）为提供数据，研究方法和领导 BACPAC倡议更广泛。