Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study

Todd B. Monroe, John C. Gore, Stephen P. Bruehl, Margaret M. Benningfield, Mary S. Dietrich, Li Min Chen, Paul Newhouse, Roger Fillingim, BettyAnn Chodkowski, Sebastian Atalla, Julian Arrieta, Stephen M. Damon, Jennifer Urbano Blackford, Ronald L. Cowan

Neuroimaging studies in younger adults have demonstrated sex differences in brain processing of painful experimental stimuli. Such differences may contribute to findings that women suffer disproportionately from pain. It is not known whether sex-related differences in pain processing extend to older adults. This cross-sectional study investigated sex differences in pain reports and brain response to pain in 12 cognitively healthy older female adults and 12 cognitively healthy age-matched older male adults (age range 65-81, median = 67). Participants underwent psychophysical assessments of thermal pain responses, functional MRI, and psychosocial assessment. When compared to older males, older females reported experiencing mild and moderate pain at lower stimulus intensities (i.e., exhibited greater pain sensitivity; Cohen's d = 0.92 and 0.99, respectively, p < 0.01) yet did not report greater pain-associated unpleasantness. Imaging results indicated that, despite the lower stimulus intensities required to elicit mild pain detection in females, they exhibited less deactivations than males in regions associated with the default mode network (DMN) and in regions associated with pain affect (bilateral dorsolateral prefrontal cortex, somatomotor area, rostral anterior cingulate cortex (rACC), and dorsal ACC). Conversely, at moderate pain detection levels, males exhibited greater activation than females in several ipsilateral regions typically associated with pain sensation (e.g., primary (SI) and secondary somatosensory cortices (SII) and posterior insula). Sex differences were found in the association of brain activation in the left rACC with pain unpleasantness. In the combined sample of males and females, brain activation in the right secondary somatosensory cortex was associated with pain unpleasantness. Cognitively healthy older adults in the sixth and seventh decades of life exhibit similar sex differences in pain sensitivity compared to those reported in younger individuals. However, older females did not find pain to be more unpleasant. Notably, increased sensitivity to mild pain in older females was reflected via less brain deactivation in regions associated with both the DMN and in pain affect. Current findings elevate the rACC as a key region associated with sex differences in reports of pain unpleasantness and brain deactivation in older adults. Also, pain affect may be encoded in SII in both older males and females.