Elevated translocator protein in skull bone marrow is linked to human chronic pain
Abstract
The skull bone marrow (SBM) is emerging as a critical hub for neuroimmune signaling, yet its role in chronic pain is unknown. Using integrated positron emission tomography/magnetic resonance imaging, here, we show that the levels of 18-kilodalton translocator protein (TSPO), a putative marker of immune cell density, are elevated in the SBM of individuals with chronic pain [ n = 125; chronic low back pain (cLBP), n = 88; knee osteoarthritis (KOA), n = 37] compared with healthy controls ( n = 22). These elevations were widespread, generally more pronounced for KOA than cLBP, associated with pain and pain-comorbid symptoms in partially segregated spatial patterns, and supported by preliminary immunohistochemical evidence in human SBM samples from a donor with a history of chronic pain (compared with a healthy donor). Because TSPO is highly expressed in myeloid cells, these results link SBM immune dysregulation with chronic pain and its associated psychological and functional impairments. These findings provide a strong rationale for investigating this previously overlooked structure, which remains largely underexplored in the context of pain.
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Authors: Mehrbod Mohammadian, Nikos Efthimiou, Katherin A. Gabriel, Ludovica Brusaferri, Joya Cooper-Hohn, Minhae Kim, Jennifer Murphy, Zeynab Alshelh, Grace Grmek, Jack H. Schnieders, Courtney A. Chane, Thomas S. Carmichael, Danika Yang, Julia Schubert, Federico E. Turkheimer, Rafael Alves Cazuza, Peter M. Grace, Ciprian Catana, Steven M. Stufflebeam, Robert R. Edwards, Vitaly Napadow, Kimberly Sullivan, Matthias Nahrendorf, Theodore J. Price, Jodi M. Gilman, Marco L. Loggia
Institutions: Brigham and Women's Hospital, Harvard University, Boston University, The University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, King's College London, London South Bank University, The University of Texas at Dallas, Spaulding Rehabilitation Hospital, Center for Systems Biology, Athinoula A. Martinos Center for Biomedical Imaging