The Placebo Hypoalgesic Response Is Reduced in Healthy Older Adults Showing a Decline in Executive Functioning

Aging is accompanied by various changes in pain perception and modulation. However, the influence of older age - and associated neurocognitive changes - on placebo hypoalgesia has not been systematically investigated. Findings to date are inconclusive, ranging from a reduced, to a preserved or even an amplified response in older adults. The aim of this study was to examine age-related changes in the placebo hypoalgesic response magnitude, and the potential modulating effect of executive functions, namely working memory, cognitive flexibility and inhibitory control.

Thirty-nine younger (18-36 years) and 42 healthy older adults (60-82 years) completed a series of executive functioning tests. Placebo hypoalgesic responding was assessed via a sham transcutaneous electrical nerve stimulation (TENS) intervention while participants received moderately painful electrical stimuli to their arm. An electroencephalogram (EEG) was recorded during the placebo paradigm and pain ratings were collected.

Overall, both age groups showed similar robust placebo hypoalgesic effects: pain ratings and pain-related brain potentials were significantly reduced in response to the sham treatment. Interestingly, worse executive functions in older adults (in particular, working memory and cognitive flexibility) were associated with reduced placebo responses. Moreover, executive functions also moderated the overall age group difference in placebo hypoalgesia: when cognitive flexibility and inhibitory control scores were low, older adults showed a smaller placebo response than younger adults.

We demonstrated an age-related reduction in placebo hypoalgesia in older adults showing a decline in executive functioning. This is an important finding, considering the fact that placebo effects contribute to positive treatment outcomes. Our results advocate the assessment of executive functions when investigating the influence of aging on placebo effects, as variable aging trajectories of decline may influence overall group comparisons.