Effect of aging on the cerebral processing of thermal pain in the human brain.

The perception of pain changes as people age. However, how aging affects the quality of pain and whether specific pain-processing brain regions mediate this effect is unclear. We hypothesized that specific structures in the cerebral nociceptive system mediate the effect of aging on the variation in different pain psychophysical measures. We examined the relationships between painful heat stimulation to the foot and both functional magnetic resonance imaging signals and gray matter volume in 23 healthy subjects (aged 25∼71 years). Increased age was related to decreased subjective ratings of overall pain intensity and the "sharp" quality of pain. Group activation maps of multiple linear regression analyses revealed that age predicted responses in the middle insular cortex (IC) and primary somatosensory cortex (S1) to pain stimuli after controlling for their gray matter volumes. Blood oxygenation level-dependent signals in the contralateral middle IC and S1 were related to ratings of "sharpness," but not any affective descriptors of pain. Importantly, activity in the contralateral middle IC specifically mediated the effect of age on overall pain perception, whereas activity in the contralateral S1 mediated the relationship between age and sharp sensation to pain. The analyses of gray matter volume revealed that key nociceptive cerebral regions did not undergo significant age-related gray matter loss. However, the volume of the cingulate cortex covaried with pain perception after adjusting for corresponding neural activity to pain. These results suggest that age-related functional alterations in pain-processing regions are responsible for changes in pain perception during normal aging.