Evidence for a role of skull bone marrow in human chronic pain as revealed by TSPO PET imaging

The skull bone marrow is emerging as a critical hub for neuroimmune signaling in various disorders, with the potential to reshape how we understand brain-immune interactions. However, 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 patients 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 very 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.