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.
Subanesthetic nitrous oxide (N2O) alters visual experience by reconfiguring large-scale brain networks rather than changing early visual processing. In a placebo-controlled fMRI study with 13 healthy adults, participants viewed a flashing checkerboard and rated visual intensity and unpleasantness. Increased unpleasantness under N2O was linked to reduced connectivity between the right anterior insula and the anterior cingulate cortex and lateral occipital cortex. Network analyses revealed reduced modularity and a collapse of hierarchical organization, with sensorimotor connectivity redistributed toward salience and associative networks. These findings suggest that altered visual experience under N2O arises from disrupted salience integration and increased cross-network communication.