Clinical Research medRxiv (all subjects)

Neural Alterations in Chronic Pain: MRI Analysis

chronic painMRIfunctional connectivitygray matter

Chronic pain is a major clinical challenge affecting hundreds of millions worldwide, yet its neural underpinnings remain incompletely understood. Previous studies have implicated a core set of brain regions—including the insula, cingulate, and somatosensory cortices—but findings on other regions and connectivity patterns have been inconsistent. This study aimed to characterize resting-state functional connectivity and gray matter volume differences between chronic pain patients and pain-free controls using a secondary analysis of publicly available data.

Anatomical and resting-state functional MRI data were analyzed from 56 patients with chronic knee pain due to osteoarthritis and 20 pain-free controls. Group comparisons were performed using Network-Based Statistic (NBS) and Bayesian multivariate regression models, with demographic covariates controlled. Results showed that approximately 75% of parcellated brain regions in the pain group exhibited increased functional connectivity compared to controls. The 30 highest degree centrality regions within the NBS network clustered in areas consistent with prior pain neuroimaging findings. Additionally, chronic pain patients exhibited reduced gray matter volume (mean -3.98%; SD 1.2%) across 33% of parcellated brain regions, including key pain-processing areas.

These findings demonstrate widespread functional and anatomical neural alterations in chronic pain, revealing a global pattern of reorganization that extends beyond previously reported network-pair effects. Such comprehensive characterization may contribute to the ongoing search for robust neuroimaging markers of chronic pain, with potential translational relevance for diagnosis and treatment monitoring.

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