The Impact of Sleep Disturbances on Endogenous Pain Modulation: A Systematic Review and Meta-Analysis

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep -related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre -/post -sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, metaanalysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. Perspective: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex -specific effects were observed, with females presenting sleep -related impaired pain inhibition but not males. (R) 2023 Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc