Neurobiological Phenotyping Core

项目总结/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 一个多学科的团队，在开发和大规模实施最先进的 方法探讨慢性疼痛的神经生物学机制。其中包括功能性磁性 共振成像（fMRI），定量感觉测试（QST），以及炎症和自主神经功能的测量。 神经系统功能为了支持UM MRC，将并行使用这些方法来识别密钥 慢性腰痛（cLBP）的神经生物学标志物，可用于推断治疗方法 可能在不同的患者内型中起作用-这是精准医学和BACPAC倡议的最终目标。 这些分析将有助于确定多种治疗方法如何独特地影响疼痛机制，这是治疗疼痛的关键一步。 开发新的有效止痛药。NPC非常适合在cLBP中进行机制研究， 因为我们已经在临床和机制研究中使用我们的方法近二十年， 和中枢神经生物学特征在各种慢性疼痛条件下，包括cLBP。因为 慢性疼痛的复杂性，我们认为，全面了解疼痛机制在临床 对于改善疼痛管理至关重要。该核心与临床和 行为研究表型和信息学核心，将主要用于促进本拟议目标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的具体目的是：1）在cLBP中进行干预反应表型分析 患者（n=500）。我们将在一组cLBP患者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cLBP有效的干预措施，包括： 治疗，物理治疗和运动，度洛沙汀，加巴喷丁或自我指压; 2）证明， 目前可用的临床衍生测量可以预测对上述治疗的不同反应性。 我们将利用目标1中的研究来确定常用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， 评估疼痛机制的问卷调查，以及背部和骨盆的结构成像; 3）进行深 Aim中描述的干预反应表型研究中个体亚组的表型分析 1、确定新的实验措施，包括：功能性神经影像学、QST、炎症和自主神经功能 我们的研究可以预测对我们的治疗的不同反应，以及推断 治疗组（n=200）。国家方案协调员将侧重于目标1和目标2中较大群体的200人的一个子集， 并进行扩展表型研究，这些研究将在每个12周治疗期之前和 接受任何介入手术; 4）提供数据，研究方法和领导， 更广泛的BACPAC倡议。

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.