Patterns and trajectories of peripheral inflammatory cytokines, immune tolerance, and lymphocyte differentiation predict transition from acute to chronic low back pain in a sex- and age-specific manner.
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2025-10
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The immune system mediates pain perception in preclinical models. Yet, the role of the immune system in transition to a chronic pain state in humans remains unclear, and biomarkers to inform the clinical management and/or development of therapies to prevent chronic pain are needed. We leveraged peripheral blood from 2 community-based cohorts of adults with an acute low back pain (LBP) episode (n = 108) to define the relationship(s) between the transition to chronic LBP and peripheral inflammation, immune cell phenotypes and functionalities, and their trajectories. Distinct patterns of baseline plasma cytokine profiles associated with transition to chronic LBP in a sex-dependent manner, of which lower IFN-β and TNF and higher IL-18 and BDNF were associated with chronic LBP development. Analysis of peripheral immune cells uncovered relationships between monocyte, T-cell, and B-cell inflammation and transition to chronic LBP that were influenced by both sex and age. It revealed relatively tolerized immune responses in participants who did not transition to chronic LBP. Baseline inflammatory cytokine and immune cell features improved the prediction of the transition to chronic LBP relative to established self-reported pain measures alone. While perceived pain at baseline was more strongly associated with immune cell phenotypes, B-cell maturation trajectories uniquely predicted transition to chronic LBP independent of self-reported pain intensity/frequency, sex, and age. Collectively, these data demonstrate that distinct patterns of peripheral inflammation are associated with the transition to chronic LBP and point towards a unique association between B-cell maturation and the development of a chronic pain state.Type
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Brown, Michael C, Andrzej S Kosinski, Rebecca Fillipo, Georgia Howell, Minh-Huy Giang, Micah Hurewitz, William Kornahrens, Colleen A Burke, et al. (2025). Patterns and trajectories of peripheral inflammatory cytokines, immune tolerance, and lymphocyte differentiation predict transition from acute to chronic low back pain in a sex- and age-specific manner. Pain. 10.1097/j.pain.0000000000003811 Retrieved from https://hdl.handle.net/10161/33644.
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Scholars@Duke
Michael Brown
Dr. Brown’s research focuses on leveraging intratumor innate immunity for cancer immunotherapy, particularly in the context of malignant brain tumors. Dr. Brown's lab uses mouse cancer models, ex vivo human tumor slice culture assays, and clinical trial associated specimens to decode mechanisms by which intratumor innate immune cells control cancer immune surveillance and develop novel in situ vaccine approaches that engage endogenous antitumor T cells. The Brown lab also collaborates with clinicians and other research groups to facilitate the translation of novel therapies, define determinants of successful immunotherapy, and elucidate mechanisms explaining immune dysfunction in patients with cancer.
Andrzej Stanislaw Kosinski
Statistical methodology for evaluation of diagnostic tests
Adjustment for misclassification
Missing data
Clinical trials
Analysis of cardiovascular and stroke data
Rebecca Fillipo
Rebecca Fillipo is a PhD student in Population Health Sciences interested in advancing methods to study the impact of climate change on health outcomes.
Steven Zachary George
Dr. George’s primary interest is research involving biopsychosocial models for the prevention and treatment of chronic musculoskeletal pain disorders. His long term goals are to 1) improve accuracy for predicting who is going to develop chronic pain; and 2) identify non-pharmacological treatment options that limit the development of chronic pain conditions. Dr. George is an active member of the American Physical Therapy Association, United States Association of the Study of Pain, and International Association for the Study of Pain.
Dr. George’s research projects have been supported by the National Institutes of Health, Department of Defense, and Orthopaedic Academy of the American Physical Therapy Association. Dr. George and his collaborators have authored over 330 peer-reviewed publications in leading medical, orthopaedic surgery, physical therapy, rehabilitation, and pain research journals. He currently serves as Editor-in-Chief for the Physical Therapy & Rehabilitation Journal. Dr. George has also been involved with clinical practice guideline development for the Academy of Orthopaedic Physical Therapy and the American Psychological Association.
Dr. George has been recognized with prestigious research awards from the American Physical Therapy Association, American Pain Society, and International Association for the Study of Pain. For example from the American Physical Therapy Association: he was named the 21st John H.P. Maley Lecturer, recognized as a Catherine Worthingham Fellow in 2017, and selected for the Marian Williams Award for Research in Physical Therapy in 2022.
Flavia Penteado Kapos
Adam Payne Goode
Dr. Goode is an Associate Professor in the Department of Orthopedic Surgery. He is a physical therapist by clinical training and epidemiologist by scientific training. His focus is on understanding the etiology of low back pain and other chronic musculoskeletal conditions and improving the delivery of care for patients with acute and chronic musculoskeletal conditions. In his research he has published in the areas of the relationship between individual radiographic features in the lumbar spine and clinical symptoms, biomarkers and peripheral joint osteoarthritis.
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