Structural and functional characterization of nucleus accumbens as a potential biomarker of the transition from acute to chronic pain after thoracoscopic surgery

Abstract Purpose Chronic postsurgical pain (CPSP) poses substantial therapeutic and preventive challenges as a common postoperative complication. Identifying predictive biomarkers could enable early intervention in high-risk patients. Preclinical evidence indicates that the nucleus accumbens (NAc) plays a key role in pain chronification, yet human neuroimaging data for CPSP are scarce. This prospective cohort study characterized longitudinal structural and functional alterations in NAc subregions as potential biomarkers for CPSP development after thoracoscopic surgery. Methods Forty patients underwent multimodal magnetic resonance imaging (MRI), including resting-state fMRI, diffusion tensor imaging, T1-weighted imaging) and clinical assessments at acute (≤ 1 week) and chronic (12 weeks) postoperative phases. Based on the diagnostic criteria for CPSP, thirteen patients developed CPSP at 12 weeks. Results CPSP group patients displayed elevated pain catastrophizing scores despite comparable acute pain intensity, indicating maladaptive affective processing. Compared to non-CPSP controls, CPSP patients exhibited significantly reduced slow-5 band fractional amplitude of low-frequency fluctuation (fALFF) in bilateral NAc shell and core subregions during both phases. Decreased functional connectivity between shell and core emerged specifically at 12 weeks. Reduced gray matter density (GMD) and inferomedial atrophy were observed in bilateral NAc of CPSP patients at both timepoints. Early postoperative bilateral NAc GMD and NAc shell fALFF correlated with subsequent pain intensity and predicted CPSP development with high discriminative accuracy, particularly when combined. Conclusions These findings establish NAc structural and functional alterations as promising neuroimaging biomarkers for CPSP susceptibility, revealing a unified neurobiological mechanism underlying affective dysregulation and pain chronification. Trial registration Registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=131606 ) with No. ChiCTR2100049631, on August 7, 2021.