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ObjectivesThis systematic review examined studies that used mediation analysis to investigate the mechanisms of action of cognitive-behavioral, mind-body, and exercise-based interventions for pain and disability in people with chronic primary musculoskeletal pain.Materials and methodsWe searched 5 electronic databases for articles that conducted mediation analyses of randomized controlled trials to either test or estimate indirect effects.ResultsWe found 17 studies (n=4423), including 90 mediation models examining the role of 22 putative mediators on pain or disability, of which 4 had partially mediated treatment effect; 8 had mixed results, and 10 did not mediate treatment effect. The conditions studied were chronic whiplash-associated pain, chronic low back pain, chronic knee pain, and mixed group of chronic primary musculoskeletal pain.DiscussionWe observed that several of the studies included in our systematic review identified similar mechanisms of action, even between different interventions and conditions. However, methodological limitations were common. In conclusion, there are still substantial gaps with respect to understanding how cognitive-behavioral, mind-body, and exercise-based interventions work to reduce pain and disability in people with chronic primary musculoskeletal pain.

Original publication




Journal article


The clinical journal of pain

Publication Date





502 - 509


Nucleus of Neuroscience and Behavior and Nucleus of Applied Neuroscience.


Humans, Exercise Therapy, Cognition, Randomized Controlled Trials as Topic, Musculoskeletal Pain, Chronic Pain