Clinical Phenotypes Supporting the Relationship Between Sleep Disturbance and Impairment of Placebo Effects

Lack of good sleep or insomnia can lead to many health issues, including an elevated risk of cardiovascular disease, obesity, fatigue, low mood, and pain. While chronic pain negatively impacts sleep quality, the relationship between descending pain modulatory systems like placebo effects and sleep quality is not thoroughly known. We addressed this aspect in a cross-sectional study in participants with chronic pain. Placebo effects were elicited in a laboratory setting using thermal heat stimulations delivered with visual cues using classical conditioning and verbal suggestions. We estimated the levels of insomnia severity with the Insomnia Severity Index and the sleep quality with the Pittsburg Sleep Quality Index. The previous night's sleep continuity was assessed as total sleep time, sleep efficiency, and sleep midpoint the night before the experiment. 277 people with chronic pain and 189 pain-free control individuals participated. Participants with chronic pain and insomnia showed smaller placebo effects than those with chronic pain without insomnia. Similarly, poor sleep quality was associated with reduced placebo effects among participants with chronic pain. Clinical anxiety measured by Depression Anxiety Stress Scales partially mediated these effects. In contrast, placebo effects were not influenced by the presence of insomnia or poor sleep quality in pain-free participants. Sleep continuity the night before the experiment did not influence the placebo effects. Our results indicate that participants who experience insomnia and/or poor sleep quality and chronic pain have smaller placebo effects, and that the previous night sleep continuity does not influence the magnitude of placebo effects. PERSPECTIVE: This study examined the relationship between sleep disturbances and experimentally induced placebo effects. We found that individuals with chronic pain who experience insomnia and poor sleep quality demonstrated reduced placebo effects compared to their counterparts with good sleep quality and no insomnia.