VBM group by age interaction analysis of gray matter. A) Significant gray matter cluster included bilaterally the insula, basal ganglia, superior temporal cortex, and ventrolateral prefrontal cortex (VLPFC) (t = 5.12, p < 0.001, cluster size 27,944 voxels; MNI coordinates at peak − 57, − 42, 21). B) The amount of gray matter was extracted for each participant from the cluster (average value over entire cluster) that was significant in the group by age interaction analysis and plotted against age. The regression lines of patients (r = − 0.73, p < 0.001) and controls (r = 0.168, p = 0.393) crossed at age 50.2 (red line). Therefore, age 50 was chosen to split the study sample into “younger” (< 50) and “older” (> 50) subjects. Controlling for pain duration and/or menopausal status did not change the age where the regression lines crossed. Controls, open circles, dotted line; patients, full circles, full line; a.u., arbitrary unit. Please note that the gray matter plotted against age is derived from a cluster consisting of subcortical and cortical brain regions, with a significant contribution from the basal ganglia. This is important because while it is correct that the volume of the neocortex usually decreases with age (except possibly the ventral ACC ()), recent studies have shown a different trajectory (mostly gray matter increases with age) for some subcortical regions and in fact primarily for the basal ganglia and hippocampal regions ().