Pain-related Post-exertional Malaise In People With Myalgic Encephalomyelitis/chronic Fatigue Syndrome And Fibromyalgia: A Meta-analysis

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic pain symptoms are prevalent. Post-exertional malaise (PEM), a phenomenon where symptom severity is worsened 24 hr or longer following physical stress, is a common occurrence in these illnesses. Fatigue is most frequently associated with PEM, but pain symptoms may also be involved. PURPOSE: Quantify the population effect of aerobic exercise on pain symptom severity in ME/CFS and FM compared to healthy adults. METHODS: We conducted a meta-analysis of case-control studies measuring pain symptoms before and after exposure to a standardized aerobic exercise test in adults with ME/CFS and FM. Hedges' d effect sizes were aggregated using random effects models and potential moderators were explored via meta-regression analysis. Results were adjusted for nesting effects using three-level modeling. RESULTS: Forty-five effects were extracted from 15 studies and the final analysis involved 306 patients (mean ± SD age = 43.1 ± 6.4 years; body mass index = 26.2 ± 1.6 kg/m2; percent female = 88.8 ± 14.6%) and 292 healthy controls (age = 41.9 ± 6.3 years; body mass index = 24.5 ± 1.2 kg/m2; percent female = 86.9 ± 17%). After adjusting for nesting effects, we observed a significant mean effect (P = 0.001, z = 3.18) indicating higher post-exercise pain in patients than controls (Hedges' d = 0.42; 95% CI: 0.16, 0.67). The mean effect was significantly moderated by pain measurement timepoint (b = -0.19, z = -2.57, P = 0.01) such that studies measuring pain 8-72 hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2 hr post-exercise (d = 0.32, 95% CI = 0.10-0.53). CONCLUSIONS: People with ME/CFS and FM experience small-to-moderate increases in pain severity following aerobic exercise. These findings confirm pain as a component of PEM and further emphasize the debilitating impact of this psychobiological phenomenon in ME/CFS and FM. Future work is needed to determine the time-course and mechanisms of pain-related PEM and develop exercise prescriptions that minimize symptom exacerbation in these individuals. Supported by U.S. Department of Veterans Affairs (VA) grant IK2 CX001679. The contents do not represent the views of the U.S. government or VA.