(175) Mechanisms between Sleep and Pain – What Do We Know from Studies of Mediation?

Evidence supports a bidirectional relationship between characteristics of sleep and pain, however prospective and microlongitudinal studies suggest that sleep has a stronger effect on pain rather than vice versa. To develop an understanding of how changes in aspects of sleep may influence pain intensity, studies which support causal inference are required. Results from such studies may provide evidence to inform the design and evaluation of hybrid interventions for pain patients that include a sleep improvement intervention. Mediation analysis is a statistical approach that enables the effect of an exposure on outcome through an intermediary variable to be assessed and quantified. Since its inception this type of analysis has been applied to a range of healthcare-related questions. Over time, methods of mediation analysis have evolved to support stronger arguments for causality, and criteria have been developed to enable the assessment of the quality of studies applying the approach. While studies of mediation applied to the sleep-pain relationship have been undertaken, to date synthesis of the evidence and an appraisal of the application of the methodologies used has yet to be published. The aim of this systematic review was, therefore, to identify studies that have investigated mechanisms underpinning the sleep-pain relationship, summarise their findings, and appraise their methodologies. Our search yielded nine papers, eight of which investigated the sleep-to-pain relationship (11 models), and two of which investigated the pain-to-sleep relationship (two models). Identified mediators included affect and mood, symptoms of depression and anxiety, attention to pain, pain helplessness, fatigue, and cortisol reactivity. However, methodological limitations were common across studies and causal inference relatively weak. We therefore use the current evidence base to suggest recommendations for the conduct of studies of mediation in the sleep and pain field moving forward.