Brain Structural Biomarkers of Risk and Resilience to Pain Chronification

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PROJECT SUMMARY Chronic pain is highly prevalent and costly to individuals and society. Once chronic, pain is very hard to treat or reverse making early identification key for prevention and early treatment to improve long-term outcomes. Recent brain imaging data from our lab as well as others have provided evidence that the structural properties of the limbic brain, such as the volume and/or shape of nucleus accumbens (NAc), amygdala, and hippocampus can predict the likelihood of “chronification” of low-back pain after an episode of sub-acute low back pain (SBP) (duration 6-12 weeks). The role of the limbic brain in predicting vulnerability or resilience to chronic pain fits with the general understanding that chronic pain is partly due to an interaction between peripheral nociceptive input and vulnerable limbic brain circuitries, which are known to mediate the negative affective and aversive learning associated with chronic pain. Hence, understanding how the structural properties of the limbic brain circuitries predict risk or resilience to chronic pain in humans is innovative and has high translational significance. However, the brain imaging studies of the transition to chronic pain remain very limited in number and scope and, hence, we still have a poor understanding of the exact limbic circuitry and structural connectivity underlying risk of or resilience to chronic pain. To date, only one small study reported that local white matter properties can predict resilience to pain chronification. Furthermore, no brain imaging study of pain chronification investigated the role of important biological variables like sex or established clinical phenotypes like the presence or absence of a neuropathic component of the low back pain. Therefore, the overarching aim of this proposal is to use state of the art structural mapping techniques to study local anatomical properties (e.g. volume, shape, neurite orientation) and white matter connectivity to identify biomarkers for pain chronification. We will use 2 different approaches, one based on biologically plausible hypotheses, and one based on data driven hypotheses identified in our preliminary data. In addition, the proposal will explore the effect of sex and clinical low-back pain phenotypes on theses biomarkers. We will recruit SBP patients and obtain brain anatomical and multi-shell diffusion weighted imaging data at baseline and at 6 months follow-up. Patients will be classified as recovered or persistent after the follow-up visit. Aim 1 will test baseline local and global gray, white matter differences between recovered and persistent patients in areas of the limbic brains like NAc, amygdala, hippocampus, anterior cingulate cortex, and white matter pathways known for their role in chronic pain (e.g., the cingulum bundle and internal capsule) and assess whether these measures change at follow-up. Aim 2 will use a data- driven approach to examine global and local gray, white matter properties predicting risk or resilience to chronic pain. Finally, aim 3 will explore the effect of sex and presence or absence of radiculopathy symptoms on the biomarkers identified in Aims 1 and 2.