Imprints of chronic pain trajectories on brain volume and tissue properties

Despite advances in understanding the mechanistic underpinnings of chronic pain (CP) conditions, knowledge on the brain anatomy microstructure associated to CP trajectories is still scarce. We sought to fill this knowledge gap by combining longitudinal self-reported CP assessments with brain imaging in a community dwelling adult population (n = 976). Aiming to provide anatomical insights beyond morphometry (based on T1 brain images), we analyzed the derived relaxometry measures MTsat, R1 and R2* and we could investigate myelin and iron content. Participants were divided in three groups according to persistent, resolved or new CP and were compared to those without CP at timepoint. Participants with persistent CP exhibited lower grey matter (GM) in fronto-temporal cortical regions and reduced myelin-related signal in subcortical and thalamic areas, alongside higher iron-sensitive metrics in the entorhinal cortex. Those who recovered from CP showed reduced cortical GM and myelin encompassing subcortical nuclei, thalamus, frontal, parietal, and temporal regions. New-onset CP participants displayed reduced GM in cortical areas. Overall, we observed reduced GM volume in a widespread network of fronto-temporal cortical areas in participants with current, resolved and new-onset CP. Myelin-related metrics were lower in the subcortical nuclei and thalamus in participants with persistent and -to a greater extent- with resolved CP, whilst persistent CP was associated with higher iron-sensitive metrics in the entorhinal cortex. Hence, CP trajectories appear to leave differential imprints on brain morphometry and tissue microstructure, with each trajectory associated with distinct non-overlapping spatial and temporal patterns in GM, myelin, and iron content.