Mehrbod Mohammadian, Nikos Efthimiou, Katherin Gabriel, Ludovica Brusaferri, Joya Cooper-Hohn, Minhae Kim, Jennifer P Murphy, Zeynab Alshelh, Grace Grmek, Jack H Schnieders, Courtney A Chane, Thomas G Carmichael, Danika Yang, Julia J Schubert, Federico E Turkheimer, Rafael A 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
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.