JAK-STAT pathway inhibition modulates centrally sensitised default mode network hubs in rheumatoid arthritis pain
medRxiv July 14, 2026 Kristian Stefanov, Joel T. Parkinson, Flavia Sunzini et al.
Peripheral inflammation can promote nociplastic pain by sensitizing the central nervous system. In rheumatoid arthritis, JAK-STAT pathway inhibitors shifted inferior parietal lobule–insula connectivity toward a normal pattern, an effect not seen with placebo or anti-TNF therapy. Transcranial magnetic stimulation of the default mode network altered its connectivity and reduced a marker of immune activation, suggesting a bi-directional brain–immune circuit. These findings provide the first human experimental evidence that peripheral JAK-STAT pathways contribute to nociplastic pain in immune-mediated inflammatory diseases.