Individual and sex-related differences in pain and relief responsiveness are associated with differences in resting-state functional networks in healthy volunteers

Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex-related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting-state network. In men, pain measures correlated with increased connectivity within the visual resting-state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions. Functional connectivity at rest predicts individual and sex-related differences in pain ratings collected outside the scanner. Across the whole group, pain ratings are associated with decreased connectivity between brain regions belonging to the default mode and the visual resting-state network. Pain sensitivity is associated with increased functional connectivity within the visual resting state network in men, and decreased connectivity between this network and prefrontal brain regions in women.