Angela R. Starkweather, Ph.D. - US grants

DESCRIPTION (provided by applicant): Low back pain is the second most frequently diagnosed pain condition in the United States and even after receiving health care treatment an estimated 40% of patients will experience persistent low back pain. Accurate detection of patients at increased risk for persistent low back pain and the delivery of effective interventions could save the United States billions of dollars each year in health care expenses and lost productivity, and improve quality of life for millions of Americans. Although a precise structural etiology of persistent low back pain is rarely present, recent studies report functional alteration in the peripheral and central nervous system of patients with persistent low back pain that are associated with enhanced pain sensitivity. It has recently been shown that genetic polymorphisms and modifications in gene expression patterns can influence pain sensitivity; however, this has never been studies in patients with low back pain. Therefore, the proposed study will investigate the role of enhanced pain sensitivity on the risk of persistent LBP through characterization of pain sensitivity and pain-sensitivity candidate gene profiling.

Abstract (Administrative Core) The Administrative Core is central to achieving the overall specific aims of the Center for Accelerating Precision Pain Self-Management (CAPPS-M). The management of resources is the focus of this core in the context of self-management of pain using the paradigm of self-management as explicated by the Individual and Family Self Management Theory (IFSMT), common data elements (CDEs) and centralized processes. This focus forms the crux of how the research generated by the pilot projects and other products of the CAPPS-M advance the science of pain self-management. We will build on our experiences and on the science generated by members of our administrative core. According to the IFSMT, self-management is a process by which individuals and families use knowledge and beliefs, self-regulation skills and abilities and social facilitation to engage in self-management behaviors with the goal of achieving optimal symptom management and quality of life1. Self-management is uniquely applicable to managing the symptom of pain across the lifespan and particularly suited to interdisciplinary research. The CAPPS-M will provide an infrastructure to facilitate the collaboration of scientists who will advance the science of pain self-management.  

Abstract Yoga has been shown to have consistent but modest effects in reducing pain and improving function in populations with chronic low back pain (CLBP) in multiple randomized controlled trials. Reviews and practice guidelines support yoga as an evidence-based treatment for CLBP with at least moderate benefit and yoga is being increasingly applied as an integrative therapy. However, the mechanisms through which yoga exerts clinical improvements on pain severity and interference have not been identified; such identification might lead to optimizing yoga interventions to improve their potency. To identify underlying mechanisms associated with yoga interventions (PA 18-323) and based on a comprehensive theoretical emotion regulation model of yoga developed by the PI, we aim to test emotion regulation as a primary mechanism of yoga's effects, and to test biological pathways through which yoga's effects on increased adaptive emotion regulation may operate to affect pain-related functioning. Emotions strongly influence perceptions of pain intensity and predict disability, particularly among individuals with CLBP, and interventions that promote emotion regulation skills have been shown to reduce pain. Increasing evidence demonstrates that consistent yoga practice can promote improved emotion regulation, but research has not yet tested whether the effects of yoga practice on CLBP are due to improvements in emotion regulation. To examine this issue, we will conduct a randomized controlled trial of 204 people with CLBP assessed pre-intervention, 6 weeks, post-intervention and at 3- and 6-month follow-up to test the impact of a yoga intervention on emotion regulation relative to stretching/strengthening without meditation or breathwork. Secondarily, we will also assess whether yoga's effects on CLBP (improved pain severity and functioning) are mediated by changes in emotion regulation. We also examine whether the link between emotion regulation and pain severity and functioning is moderated or mediated by pain sensitization, effects that have been theorized and/or demonstrated to account for changes in pain, thereby testing emotion regulation as a key mechanism underlying the clinical effects of yoga on CLBP.

PROJECT SUMMARY One of the most common and costly chronic pain conditions is low back pain (LBP), which produces more global disability than any other condition. Up to 39% of patients with an acute LBP episode report chronic LBP (pain lasting >3 months) and long-term disability for 2 years or longer. Increased mechanistic understanding of the transition from acute to chronic LBP will enable us to identify biomarkers early in the transition period and new therapeutic targets at critical windows of opportunity to prevent and/or better manage chronic LBP. In this study, we will test the hypothesis that neurophysiological and gene expression differences can be used to build a predictive model that will define the chronic LBP phenotype and transcriptome and identify those LBP patients who will transition from acute to chronic pain phenotypes. We will prospectively follow a cohort of 380 LBP patients and 40 healthy controls (for comparison with LBP patients and to track gene expression stability over time) for two years following the initial clinic visit for report of LBP. We will rigorously phenotype the participants, including measurement of neurophysiological factors, and analyze gene expression at baseline and regular intervals during the first year and at 18 and 24 months. We will accomplish these goals via two specific aims: Aim 1: To examine neurophysiological predictors of the transition from acute to chronic pain at baseline and over time following initial clinic visit for report of LBP. We will enroll participants at time of initial LBP and follow them 6, 8, 10, 12, 16, 20, 24, and 52 weeks, as well as 18 and 24 months? post onset. At timepoints that correspond with blood draws for RNA-seq we will conduct neurophysiological testing to characterize peripheral sensory nerve function, temporal summation (wind up) and conditioned pain modulation (intactness of the descending inhibitory pain modulatory system). At other timepoints, participants will fill out online questionnaires about pain and psychosocial constructs. Aim 2: To test the hypothesis that differential expression of MHC locus genes at baseline and over time will be associated with the risk for chronic pain, while differential expression of known pain genes will define the chronic LBP transcriptome. In this aim, we will isolate total RNA from whole blood for sequencing at baseline and 6, 12, 24, 52 weeks, and 2 years. We will examine how changes in gene expression differs in extreme phenotypes from three groups (n=20 healthy participants, n=50 acute LBP, n=50 chronic LBP) at each of the six timepoints. In addition to biomarker identification, we will conduct non-biased pathway analysis of the differentially expressed genes to gain mechanistic insight into potential novel therapeutic targets for chronic pain prevention and/or management. This study is highly aligned with NINR?s strategic plan and mission, the National Pain Strategy, IOM report, and the NIH?s HEAL Initiative to identify biomarkers of the risk for chronic pain and therapeutic pain targets.