Are there sex differences in placebo analgesia during visceral pain processing? A fMRI study in healthy subjects

BackgroundWe explored sex differences in the neural mechanisms mediating placebo analgesia in an established visceral pain model involving painful rectal distensions in healthy volunteers. MethodsN=15 men and N=15 women underwent three consecutive functional magnetic resonance imaging sessions during which cued painful rectal distensions were delivered. After an adaptation session, positive expectations were induced with deceptive instructions regarding administration of an analgesic drug (placebo session). In the other session (control), truthful information about an inert substance was given. Sex differences in placebo-induced modulation of neural activation during anticipation and pain were analyzed along with ratings of expected and perceived pain intensity. Key ResultsPlacebo-induced reductions in pain ratings were comparable between men and women. At the level of the brain, group comparisons with respect to differences between the placebo and control conditions revealed greater modulation of the posterior insula (regions-of-interest analysis: p(FWE)<0.05) and dorsolateral prefrontal cortex (whole-brain analysis: p<0.001, uncorrected) during pain anticipation in women. During pain, placebo-induced down-regulation of the insula was altered in women compared to men (ROI analysis: p(FWE)<0.05). Conclusions & InferencesOur data provide first evidence supporting sex differences in pain-induced neural modulation during visceral placebo analgesia despite similar placebo-induced reductions in perceived pain intensity. These preliminary findings might contribute to elucidating mechanisms mediating placebo effects in clinical conditions associated with chronic abdominal pain such as in irritable bowel syndrome.