Brain Correlates of Chronic Pain Onset, Progression, and Resolution

MRI-detected changes in brain structure have been reported in chronic pain patients. Whether these anomalies result from, lead to, or are merely comorbid with prolonged pain remains unclear. To investigate this relationship, we examined changes in neural imaging-derived phenotypes (IDPs) and their correlations with chronic pain trajectories. We used longitudinal data from 40,000 U. K. Biobank participants, grouping them into one of four categories: unresolved, resolved, new chronic pain, and pain-free controls in and across eight body sites (head, face, neck/shoulder, back, stomach, hip, knee, and widespread). Chronic pain status was assessed at two visits: baseline (without imaging), and follow-up (with MRI). We used multiple linear regression models (one per IDP as outcome) to estimate associations between pain trajectories and changes in brain-wide gray matter volume, cortical thickness, and surface area measures, while controlling for demographic and scanning procedure metrics. Our results show that unresolved pain is associated with widespread gray matter volume and surface area reduction in both cortical and subcortical regions; new chronic pain is associated with limited gray matter volume reduction focused in cortical regions most affected in the unresolved pain group, and no changes in subcortical regions; resolved pain is associated with surface area reduction exclusively in the somatosensory cortex. Collectively, these findings suggest a reversible spreading of gray matter loss across the brain that correlates with chronic pain duration. We have thus identified brain markers of chronic pain progression and resolution, which may be targeted in novel treatment approaches, such as neuromodulation.