دانلود رایگان مقاله انگلیسی مقاومت مسکن پلاسیبو در طول خواب: یک مطالعه آزمایشی - الزویر 2018

ABSTRACT

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.

DISCUSSION

This is the first experimental study to investigate directly placebo analgesia during sleep. Results suggest that placebo analgesia manipulations performed prior to sleep can modulate the responsiveness to nociceptive stimuli on the following night. In addition to significant nocturnal pain relief reported in the morning following the placebo treatment, participants showed fewer arousals during REM sleep, with an unexpected increase during SWS. This suggests that the lower nocturnal pain and fewer sleep disturbances reported following placebo induction may be due to effects during REM sleep but not SWS.

Several clinical trials have shown improvements in placebo groups relative to pre-treatment baseline in self-reported pain and behavioral measures of sleep interference (e.g., [21;54]; [12]; [24]). In addition, meta-analytic reviews have  confirmed robust placebo effects in diseases such as insomnia and restless legs syndrome ([40]; [47]; [7]; [23]). A study of fibromyalgia provided further evidence that changes in pain after the administration of a placebo treatment were highly correlated with measures of sleep quality and sleep disturbance ([57]), suggesting that the placebo analgesia effects may generalize to nocturnal pain and/or relate to improved sleep.