• Ellen E Barhorst, Alexander E Boruch, Dane B Cook, and Jacob B Lindheimer.
• Office of Research and Development, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
• Pain Med. 2022 May 30; 23 (6): 1144-1157.

ObjectiveMyalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon in which symptom severity is worsened for 24 hours or longer after physical stress, but the pain-related component of PEM is not well characterized.DesignSystematic review and meta-analysis.MethodsCase-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges' d effect sizes were aggregated with random-effects models, and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects with three-level modeling.ResultsForty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small to moderate effect indicating higher post-exercise pain in patients than in controls (Hedges' d = 0.42; 95% confidence interval [CI]: 0.16-0.67). The mean effect was significantly moderated by pain measurement time point (b = -0.19, z = -2.57, P = 0.01), such that studies measuring pain 8-72 hours after exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than did those measuring pain 0-2 hours after exercise (d = 0.32, 95% CI = 0.10-0.53).ConclusionsPeople with ME/CFS and FM experience small to moderate increases in pain severity after exercise, which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

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