Project Summary/Abstract Up to 25% of individuals will develop acute low back pain (LBP) each year. As many as 63% of those individuals will develop chronic LBP that persists for most or every day for several months. The reasons why some individuals transition from acute to chronic LBP are poorly defined. Our prior funding period, and work from others, have identified elevated inflammatory cytokines among individuals with chronic LBP. The reasons why inflammation persists are unknown. Our long-term goal is to discover how inflammation, regulated by the immune system, predicts the transition from acute to chronic LBP. Identifying mechanisms that regulate the inflammatory response to acute LBP and the development of chronic LBP could identify novel therapeutic targets and broadly impact the pain research field. To accomplish this goal, we will conduct an observational cohort study enrolling n=480 participants with acute LBP from two diverse communities in Durham and Cabarrus, North Carolina. At baseline, 3 months (primary endpoint), and 6 months, participants will provide a blood specimen, pressure-pain threshold testing, physical performance measurement, physical activity via actigraphy, and patient-reported questionnaires. At 12 months, survey-based measures will be collected. The rationale for this proposed research comes from our strong pilot work in that 1) identifying a change in immune cell profiles and baseline inflammatory cytokines may be important biological factors predicting persistent inflammation and chronic LBP, and 2) these responses from the immune system may be different by race (Black versus White) and 3) acute LBP transition to chronic LBP can result from biological, social, psychological domains or a combination of these sources and well-defined phenotypes from these domains could improve chronic LBP prediction. To our knowledge, we will be the first to comprehensively define the biochemical reaction and inflammatory and immune-regulated trajectories in the transition from acute to chronic LBP in a diverse community. Understanding the immune response to acute LBP would lead to new multifactorial phenotypes of LBP transitions and specific intervention targets based on phenotype composition.