Evidence for a role of skull bone marrow in human chronic pain as revealed by TSPO PET imaging
Mohammadian, M.; Efthimou, N.; Brusaferri, L.; Cooper-Hohn, J.; Kim, M.; Murphy, J. P.; Alshelh, Z.; Grmek, G.; Schnieders, J. H.; Chane, C. A.; Carmichael, T. G.; Yang, D.; Catana, C.; Stufflebeam, S. M.; Edwards, R. R.; Napadow, V.; Sullivan, K.; Nahrendorf, M.; Gilman, J. M.; Loggia, M. L.
Show abstract
The skull bone marrow 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 kDa translocator (TSPO), a marker of immune cell density, is elevated in the skull bone marrow of individuals with chronic pain (N=125; chronic low back pain [cLBP], N=88; knee osteoarthritis [KOA], N=37), compared to healthy controls (N=22). These elevations were widespread, generally more pronounced for KOA than cLBP, and associated with greater pain intensity, pain interference, depression, and anxiety (all p < 0.001). Because TSPO is highly expressed in myeloid cells, these results associate skull bone marrow 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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