Brain gray matter changes across chronic pain trajectories: MRI evidence from 35,000 individuals

Abstract Chronic pain affects brain gray matter structure, but the magnitude, pattern, and reversibility of brain changes upon pain recovery remain unclear because of inconsistent findings from small-scale studies. We analyzed data from 35,052 UK Biobank participants who completed chronic pain assessments at 2 time points, approximately 9 years apart, evaluating pain lasting 3 months or more, across 8 body sites. Brain magnetic resonance imaging data were available from the second time point. Participants were grouped into 4 categories: Pain-free controls, New chronic pain, Persistent chronic pain, and Resolved chronic pain. We examined relationships between these categories and 313 brain-wide measures across cortical surface area, cortical thickness, and subcortical volume. New chronic pain was associated with surface area reductions in sensorimotor, temporo-parietal, and medial and lateral prefrontal cortices. Persistent chronic pain showed larger and more widespread area reductions and mixed changes in cortical thickness and subcortical volumes, including cerebellar atrophy and hypertrophy in the thalamus and basal ganglia. Resolved pain demonstrated reversibility of most brain changes, except sustained surface area reductions in the primary somatosensory cortex. No areas showed effects consistent with a predisposition to pain. Brain structural changes in chronic pain reflect adaptive neuroplasticity rather than irreversible damage or preexisting vulnerability. Most changes appear reversible with pain resolution, underscoring the importance of effective pain treatment to alleviate symptoms and support recovery of brain structure and function.