Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross-Sectional Resting State Functional Connectivity Study

Objective. A long-standing hypothesis is that when compared with males, females may be at increased risk of experiencing greater pain sensitivity and unpleasantness. The purpose of this study was to examine sex differences in pain psychophysics and resting state functional connectivity (RSFC) in core pain regions in an age-and sex-matched sample of healthy older adults. Design. Between groups, cross-sectional. Setting. Vanderbilt University and Medical Center. Subjects. The sample in the analyses reported here consisted of 19 cognitively intact males matched with 19 cognitively intact females of similar ages (median ages: females = 70 years, males = 68 years). Methods. Psychophysical assessment of experimental thermal pain and RSFC. Results. There were no significant differences in perceptual thresholds or unpleasantness ratings in response to thermal stimuli. Older males showed greater RSFC between the affective and sensory networks and between affective and descending modulatory networks. Conversely, older females showed greater RSFC between the descending modulatory network and both sensory and affective networks. The strongest evidence for sex differences emerged in the associations of thermal pain with RSFC between the anterior cingulate cortex (ACC) and amygdala and between the ACC and peri-aqueductal gray matter in older females relative to older males. Conclusions. We found no differences in pain sensitivity or pain affect between older males and older females. Additionally, we found that older females exhibited a greater association between thermal pain sensitivity and RSFC signal between regions typically associated with pain affect and the descending modulatory system. One interpretation of these findings is that older females may better engage the descending pain modulatory system. This better engagement possibly translates into older females having similar perceptual thresholds for temperature sensitivity and unpleasantness associated with mild and moderate pain. These findings contrast with studies demonstrating that younger females find thermal pain more sensitive and more unpleasant.