People with spondyloarthritis (SpA) often continue to experience pain even when inflammation is well controlled. This suggests that factors beyond inflammation may contribute to persistent symptoms. We focused on the enthesis—the site where tendons and ligaments attach to bone—which is the primary site of inflammation in SpA and may also play an important role in pain generation.
Using immune cells isolated from human spinal enthesis tissue, we developed a laboratory model of enthesitis to investigate molecules that could link inflammation to pain. We compared the effects of two Janus kinase inhibitors (JAKi), upadacitinib (UPA) and deucravacitinib (DEU), with those of the tumour necrosis factor inhibitor adalimumab (ADA).
We identified CXCL10, an immune signalling molecule known to activate pain pathways, as a potential contributor to persistent pain. UPA markedly reduced CXCL10 production, whereas ADA did not show the same effect.
These findings suggest that JAK inhibitors may reduce pain not only by controlling inflammation but also by limiting neuro-immune signals that sensitize pain pathways. Although further studies in patients are needed, CXCL10 may represent a promising therapeutic target for persistent pain in SpA and help explain why JAK-i often provide greater pain relief than expected from their anti-inflammatory effects alone.