Precuneus hyperexcitability mediates inflammatory-driven pain hypersensitivity following sleep disruption: a multimodal neuroimaging study

BackgroundSleep disruption(SD) has been shown to amplify inflammatory signaling and promote pain hypersensitivity, but how inflammation interacts with brain functional alterations to drive pain sensitization remains unclear. This study therefore aims to investigate inflammatory associated pain hypersensitivity induced by SD and characterize neural correlates for mediating neuroimmune-pain interactions.Materials and methodsThis study employed two complementary designs: 1) A experimental design comparing forced awakening (FA) and uninterrupted sleep (US) groups, with polysomnography (PSG), task-fMRI, structural MRI, inflammatory cytokines, and quantitative sensory testing post-intervention; 2) A longitudinal cohort of chronic pain patients assessed pre- and 3-months postoperatively using neuroimaging, clinical pain metrics, and sleep quality indices (PSQI). Mass univariate analyses were performed to reveal differences in pain-elicited brain response between FA and US group. Structural and functional metrics were analyses within resultant brain regions using patient cohort. Multivariate correlations and mediation models were performed to test neuroimmune interactions.ResultsFA subjects exhibited reduced total/slow-wave sleep, elevated IL-6, and lowered pain-thresholds versus US. Task-fMRI revealed hyperactivation in the precuneus and middle temporal gyrus during pain processing after FA. Serum IL-6 inversely correlated with pain thresholds and positively with precuneus activation. Mediation analysis demonstrated a mediating effect of precuneus hyperexcitability on the IL-6-pain hypersensitivity relationship. Longitudinal data from patient cohort complemented these findings, showing aberrant precuneus normalization correlated with improvement in pain and sleep quality.ConclusionAcross experimental and clinical cohorts, we identified the precuneus as a cortical hub linking sleep disruption, inflammation, and pain hypersensitivity, thereby revealing a novel neuroimmune pathway for sleep-related pain amplification.