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Clin J Pain. 2019 Feb 28. doi: 10.1097/AJP.0000000000000697. [Epub ahead of print]

Sleep and Pain: A Systematic Review of Studies of Mediation.

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Epidemiology Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK.
Kratz Lab, Department of Physical Medicine and Rehabilitation, University of Michigan, USA.
Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, USA.
Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.
Evidence Synthesis and Modelling for health Improvement (ESMI), Institute for Health Research, College of Medicine and Health, University of Exeter, Exeter, UK.
Health Services Research Unit, University of Aberdeen, UK.
Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Department of Psychology, University of Warwick, Coventry, UK.



A relationship between sleep and pain is well established. A better understanding of the mechanisms that link sleep and pain intensity is urgently needed to optimise pain management interventions. The objective of this systematic review was to identify, synthesise and critically appraise studies that have investigated putative mediators on the path between sleep and pain intensity.


A systematic search of five electronic bibliographic databases (EMBASE, MEDLINE, CINAHL, PsycINFO and the Cochrane Central Register of Controlled Trials) was conducted. Eligible studies had to apply a formal test of mediation to variables on the path between a sleep variable and pain intensity or vice versa. All searches, data extraction and quality assessment were conducted by at least two independent reviewers.


The search yielded 2,839 unique articles, nine of which were eligible. Of 13 mediation analyses, 11 investigated pathways from a sleep variable to pain intensity. Putative mediators included affect/mood, depression and/or anxiety, attention to pain, pain helplessness, stress, fatigue, and physical activity. Two analyses investigated pathways from pain intensity to a sleep variable, examining the potentially mediating role of depressive symptoms and mood. While evidence supported a mediating role for psychological and physiological aspects of emotional experiences and attentional processes, methodological limitations were common, including use of cross-sectional data and minimal adjustment for potential confounders.


A growing body of research is applying mediation analysis to elucidate mechanistic pathways between sleep and pain intensity. Currently sparse evidence would be illuminated by more intensively collected longitudinal data and improvements in analysis.Systematic review registration: PROSPERO registration number CRD42016049240.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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