Neurobiological Phenotyping Core

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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.