Age-related differences in functional connectivity associated with pain modulation.

Growing evidence suggests that aging is associated with impaired endogenous pain modulation, and that this likely underlies the increased transition from acute to chronic pain in older individuals. Resting-state functional connectivity (rsFC) offers a valuable tool to examine the neural mechanisms behind these age-related changes in pain modulation. RsFC studies generally observe decreased within-network connectivity due to aging, but its relevance for pain modulation remains unknown. We compared rsFC within a set of brain regions involved in pain modulation between young and older adults and explored the relationship with the efficacy of distraction from pain. This revealed several age-related increases and decreases in connectivity strength. Importantly, we found a significant association between lower pain relief and decreased strength of three connections in older adults, namely between the periaqueductal gray and right insula, between the anterior cingulate cortex (ACC) and right insula, and between the ACC and left amygdala. These findings suggest that the functional integrity of the pain control system is critical for effective pain modulation, and that its function is compromised by aging.