Placebo analgesia persists during sleep: An experimental study

Although placebo analgesia is a well-recognized phenomenon with important clinical implications, the possibility that placebo effects occur during sleep has received little attention. This experimental study examined whether responsiveness to acute heat pain stimuli applied during sleep could be reduced following a placebo conditioning procedure administered before sleep. Healthy individuals (n= 9) underwent polysomnographic recordings for one habituation night followed by one placebo analgesia night and one control night in counterbalanced order. Conditioning induced robust analgesia expectations before the placebo night. In the morning after the placebo night, participants reported less nocturnal pain, anxiety, and associated sleep disturbance (all p's < 0.05) compared to the control night. Furthermore, placebo induction produced a 10% reduction in brain arousals evoked by noxious stimuli during rapid-eye-movement (REM) sleep (p= 0.03), consistent with our previous findings suggesting that analgesia expectations are reprocessed during REM sleep. In contrast, arousals increased by 14% during slow wave sleep (SWS) (p= 0.02). In the morning after the last recording night, placebo testing administered as a manipulation check confirmed that typical placebo analgesic responses were produced during waking (p's < 0.05). These results suggest that analgesia expectations developed before sleep reduced nocturnal pain perception and subjective sleep disturbances and activated brain processes that modulate incoming nociceptive signals differentially according to sleep stage. These results need to be replicated in future studies exploring how analgesia expectations may be reactivated during different sleep stages to modulate nociceptive responses.