Placebo Analgesia Conditioning is Modulated by Sleep in Healthy Individuals: Historical Perspectives and Current Directions

During sleep, experimental pain can induce arousal (transient brain, heart and muscle resurgences), a marker of sleep disruption. The pain related arousal response rate is higher in light Stage N2 sleep, lower in deep Stage N3 (i.e., slow wave sleep), and intermediate in REM sleep. Furthermore, higher thermal pain is needed to induce arousal in stage N3 and REM sleep. The effect of persuasive placebo analgesia conditioning before sleep persists during and after sleep. Shorter REM predicts placebo-induced expectations of pain relief. Use of clonidine, an alpha 2 adrenergic agonist, blunts REM sleep, which may contribute to the modulation of expectation-mediated placebo effect. Total sleep deprivation or sleep continuity disruption lowers pain threshold and disrupts endogenous analgesia mechanisms. Experimental sleep continuity disruption reduces Stage N3 and REM duration, with hyperalgesia in males and a rise in temporal summation in females. Dr. Lavigne will review the latest findings from his lab and others with regard to sleep macrostructure alterations, placebo analgesic conditioning, and endogenous pain modulation. He will argue that standardization of measurement and individual phenotyping (e.g., sex, age, comorbidities, catastrophizing, sleep efficiency) is required to dismantle the mechanisms associated with those effects mechanism in both healthy and chronic pain individuals.