Abstract
The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.
Highlights
The placebo effect is a neurobiological and psychophysiological process known to reduce pain perception
We observed that placebo analgesia improved in the morning in response to rapid eye movement (REM) sleep deprivation, and REM sleep moderated the relationship between pain relief expectations and placebo analgesia
Laverdure-Dupont and collaborators [18] demonstrated that when volunteers developed positive expectations due to persuasive conditioning and verbal suggestions before sleep, they spent less time in REM sleep, and they showed a high negative correlation between REM sleep duration and expectation-mediated placebo analgesia the day
Summary
The placebo effect is a neurobiological and psychophysiological process known to reduce pain perception. This analgesia effect is mediated through two main mechanisms, expectations and learning, which influence pain relief independently of the treatment effect itself [1]. According to the conditioning—expectancy relationship, experimental placebo tests could be designed as a series of extinction trials (i.e., conditioned stimulus presented without a decrease in nociceptive input). In this view, the maintenance of hypoalgesia reflects the preserved relief expectations preserved classical extinction processes [11]
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