Purpose Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups; however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of RPE responses to aerobic exercise in ME/CFS and FM compared with healthy adults. Methods Case–control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study’s description of participant characteristics, matching procedures, and administration of RPE scales. Hedges’ d effect sizes for RPE were calculated and aggregated using random-effects models, and potential moderators were explored with meta-regression analysis. Results Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges’ d = 0.85, 95% confidence interval = 0.62–1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (P < 0.001, R 2 = 0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b = 0.60, z = 4.6, P < 0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, P = 0.04). Conclusions People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms that could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.

Objective Myalgic 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 where symptom severity is worsened 24hr or longer following physical stress, but the pain-related component of PEM is not well characterized. Design Systematic review and meta-analysis Methods Case-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 using random effects models and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects using three-level modeling. Results Forty-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 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 8-72hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2hr 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 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.

PURPOSE: Chronic neuropathic pain(CNP) is clinically associated with the development of affective disorders such as anxiety and depression. However, the time course of CNP-induced depression symptoms remains unclear. This study set out to investigate the influence of CNP on depression-like behaviors at different periods. METHODS: CNP was induced using the model of sciatic nerve chronic constriction injury (CCI). To explore the behavioral tests at each time point after CCI, the mice were randomly assigned into the sham group and the CCI group. The CCI group was divided into six subgroups (n = 6 for each time point) at 7, 14, 21, 28,35, and 42 days after CCI, respectively. Mechanical allodynia was assessed using paw withdrawal frequency (PWF) by Von-Frey filaments (0.07g). The depression-like behaviors were examined using the forced swimming test (FST) and the tail suspension test(TST). All animal experiments were approved by the Laboratory Animal Welfare and Ethics Committee of Zhengzhou University. RESULTS: CCI mice at each time point display significantly higher basal paw withdrawal frequency (7d, 44.44%±4.12%; 14d, 48.89%±4.83%; 21d, 50.00%±4.71%; 28d,47.78%±5.21%; 35d, 42.22%±4.65%; 42d, 35.56%±2.94%) to Von-Frey filaments compared with the sham group (11.59%±2.51%,P<0.05). In the forced swim test, CCI mice spent significantly more time immobile on day 21 (135.86±27.56s), day 28 (139.6±21.29s), day 35 (155.86±21.36s), and day 42 (132.71±25.73s) than the sham group (79.18±25.96s, P<0.01). The time course of immobility in the tail suspension test was very similar to the result of FST. The immobility time of the CCI group on day 21(152.44±15.83s), day 28(148.29±29.84s), day 35(159.80±18.05s), day 42(132.71±25.73s) was significantly longer than that of the sham group(112.75±23.72s, P<0.05). CONCLUSIONS: These results demonstrated that three weeks of neuropathic pain induced depression-related behaviors. It indicates that intervention programs should be implemented in the early stage of pain to avoid depression, which has potential clinical implications.