Background Fibromyalgia (FM) patients are likely to differ from healthy controls in muscle activity and in reactivity to experimental stress. Methods We compared psychophysiological reactivity to cognitive stress between 51 female FM patients aged 18 to 65 years and 31 age- and sex-matched healthy controls. They underwent a 20-minute protocol consisting of three phases of relaxation and two phases of cognitive stress. We recorded surface electromyography normalized to maximum voluntary muscle contraction (%EMG), the percentage of time with no muscle activity (EMG rest time), and subjective pain and stress intensities. We compared group reactivity using linear modelling and adjusted for psychological and life-style factors. Results The FM patients had a significantly higher mean %EMG (2.2 % vs. 1.0 %, p < 0.001), pain intensity (3.6 vs. 0.2, p < 0.001), and perceived stress (3.5 vs. 1.4, p < 0.001) and lower mean EMG rest time (26.7 % vs. 47.2 %, p < 0.001). In the FM patients, compared with controls, the pain intensity increased more during the second stress phase (0.71, p = 0.028), and the %EMG decreased more during the final relaxation phase (-0.29, p = 0.036). Within the FM patients, higher BMI predicted higher %EMG but lower stress. Leisure time physical activity predicted lower %EMG and stress and higher EMG rest time. Higher perceived stress predicted lower EMG rest time, and higher trait anxiety predicted higher pain and stress overall. Conclusions Our results suggest that repeated cognitive stress increases pain intensity in FM patients. FM patients also had higher resting muscle activity, but their muscle activity did not increase with pain. Management of stress and anxiety might help control FM flare-ups. Trial registration Retrospectively registered on ClinicalTrials.gov (NCT03300635).

Objectives:Fibromyalgia (FM) patients have an increased risk for glucose metabolism disturbances, and impaired glucose tolerance may be associated with symptom severity. Elevated levels of plasma lactate have been detected in FM patients. Both pyruvate and lactate are produced in glucose metabolism and reflect oxidative metabolism. The objective of our study was to analyse disturbances in glucose, pyruvate, or lactate metabolism in FM patients.Methods:We measured plasma levels of glucose, pyruvate, and lactate during an oral glucose tolerance test in 40 non-diabetic, female FM patients and 30 age- and gender-matched healthy controls.Results:FM patients showed a higher glycaemic response to the glucose load at 1 hour (F [1,68] = 10.4, P = .006) and 2 hours (F [1,68] = 7.80, P = .02), and higher glucose area under the curve (13.8 [SD 2.92] vs 11.6 [SD 2.31], P < .01), than healthy controls. Group differences were explained by higher body mass index and percentage of smokers among the FM patients. Pyruvate and lactate levels were similar in both groups.Discussion:Impaired glucose regulation in FM patients is likely not due to FM itself, but to associated lifestyle factors. Our results highlight the importance of assessing the glucose regulation status and the lifestyle factors affecting glucose regulation in FM patients for prevention or early treatment of diabetes and associated complications.Trial Registration:ClinicalTrials.gov (NCT03300635)

OBJECTIVES Fibromyalgia, a common pain syndrome, is thought to be a non-inflammatory, nociplastic condition but evidence implicating neuroinflammation has been increasing. Systemic inflammation may be associated with more severe symptoms in some fibromyalgia patients. We studied healthy controls and fibromyalgia patients with and without systemic inflammation detectable using high-sensitivity C-reactive protein (hsCRP) measurement. METHODS We measured hsCRP levels, and gathered clinical and questionnaire data (including Fibromyalgia Impact Questionnaire (FIQ)), from 40 female fibromyalgia patients and 30 age-matched healthy women: hsCRP &gt; 3 mg/l was considered elevated. RESULTS Fibromyalgia patients had significantly higher mean hsCRP levels than controls, explained by overweight and lower leisure-time physical activity. Eight fibromyalgia patients had elevated, and 29 normal, hsCRP. Levels of hsCRP were significantly correlated with FIQ scores. Patients with elevated hsCRP had higher FIQ scores, with worse physical functioning and greater pain, and were less likely to be in work, than patients with normal hsCRP. These patient groups did not differ by blood count, liver function, or lipid profiles, nor by education, psychological measures, sleep disturbance, smoking, or comorbidities. CONCLUSION Some fibromyalgia patients have elevated hsCRP, mostly due to overweight and physical inactivity. They have worse symptoms and their ability to work is impaired. Measurement of hsCRP may help to identify fibromyalgia patients in greatest need of interventions supporting working ability. TRIAL REGISTRATION ClinicalTrials.gov, https://clinicaltrials.gov, NCT03300635 Lay summary What does this mean for patients? People with fibromyalgia suffer from persistent pain and reduced physical functioning. Severity of fibromyalgia symptoms varies greatly between patients. Laboratory tests have not been able to confirm fibromyalgia or gauge its severity. C-reactive protein (CRP) is a commonly used indicator of inflammation; even low levels of inflammation are known to predict worse health outcomes. In our study, we measured the CRP levels of 40 female patients with fibromyalgia and collected data on their medical history and lifestyle factors. We found that patients with above normal levels of CRP had worse symptoms, lower physical functioning and were less likely to be able to work. This increased inflammation was mostly explained by being overweight and having reduced physical activity, and not by, for example, other medical conditions. Although some patients had severe symptoms without inflammation, our results suggest that a simple and widely available blood test could be useful for identifying patients with severe fibromyalgia. CRP measurements could also be used to monitor the effectiveness of lifestyle changes such as exercise and weight-loss in these individuals. Using medication to alleviate fibromyalgia symptoms through reduction of inflammation should also be studied in the future.

Fibromyalgia (FM) is associated with sympathetically dominant dysautonomia, but the connection between dysautonomia and FM symptoms is unclear. Dysautonomia can be analysed with heart rate variability (HRV) and it has been proposed that FM patients comprise subgroups with differing profiles of symptom severity. In our study, 51 female FM patients aged 18 to 65 years and 31 age-matched healthy female controls followed a 20-min protocol of alternating relaxation and cognitive stress (mental arithmetic). Heart rates and electrocardiograms were registered. The HRV measures of heart rate (HR), mean interval between heart beats (RRmean), root mean squared interval differences of successive beats (RMSSD), and the standard deviation of intervals between normal heart beats (SDNN) were analysed with generalized linear modelling. Features in HRV reactivity which differed between FM patients and controls were used to cluster the FM patients and cluster characteristics were analysed. FM patients had higher baseline HR (72.3 [SD 12.7] vs 64.5 [7.80], p < 0.001) and lower RRmean (0.844 [0.134] vs 0.934 [0.118], p = 0.002), compared with controls. They also reacted to repeated cognitive stress with an attenuated rise in HR (− 4.41 [95% CI − 7.88 to − 0.93], p = 0.013) and attenuated decrease of RRmean (0.06 [95 CI 0.03 to 0.09], p < 0.001), compared with controls. Clustering of FM patients by HRV reactivity resulted in three clusters characterised by (1) normal levels of HRV and HRV reactivity with low levels of depressive mood and anxiety, (2) reduced levels of HRV and impaired HRV reactivity with increased levels of depressive mood and high levels of anxiety, and (3) lowest HRV and most impaired HRV reactivity with the highest scores for depressive mood and anxiety. Our results show that FM patients have lower HRV than healthy controls and their autonomous reactions to cognitive stress are attenuated. Dysautonomia in FM associates with mood disturbance. Trial registration ClinicalTrials.gov (NCT03300635). Registered October 3 2017—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03300635.

Background Patients with fibromyalgia (FM) exhibit low peak oxygen uptake ($$\dot{\text{V}}$$ V ˙ O2peak). We aimed to detect the contribution of cardiac output to ($$\dot{\text{Q}}$$ Q ˙ ) and arteriovenous oxygen difference $$[\text{C}(\text{a-v})\text{O}_{2}]$$ [ C ( a-v ) O 2 ]  to $$\dot{\text{V}}\text{O}_{2}$$ V ˙ O 2 from rest to peak exercise in patients with FM. Methods Thirty-five women with FM, aged 23 to 65 years, and 23 healthy controls performed a step incremental cycle ergometer test until volitional fatigue. Alveolar gas exchange and pulmonary ventilation were measured breath-by-breath and adjusted for fat-free body mass (FFM) where appropriate. $$\dot{\text{Q}}$$ Q ˙ (impedance cardiography) was monitored. $$\text{C}(\text{a-v})\text{O}_{2}$$ C ( a-v ) O 2  was calculated using Fick’s equation. Linear regression slopes for oxygen cost (∆$$\dot{\text{V}}$$ V ˙ O2/∆work rate) and $$\dot{\text{Q}}$$ Q ˙ to $$\text{V}$$ V O2 (∆$$\dot{\text{Q}}$$ Q ˙ /∆$$\dot{\text{V}}$$ V ˙ O2) were calculated. Normally distributed data were reported as mean ± SD and non-normal data as median [interquartile range]. Results $$\dot{\text{V}}$$ V ˙ O2peak was lower in FM patients than in controls (22.2 ± 5.1 vs. 31.1 ± 7.9 mL∙min−1∙kg−1, P < 0.001; 35.7 ± 7.1 vs. 44.0 ± 8.6 mL∙min−1∙kg FFM−1, P < 0.001). $$\dot{\text{Q}}$$ Q ˙ and C(a-v)O2 were similar between groups at submaximal work rates, but peak $$\dot{\text{Q}}$$ Q ˙ (14.17 [13.34–16.03] vs. 16.06 [15.24–16.99] L∙min−1, P = 0.005) and C(a-v)O2 (11.6 ± 2.7 vs. 13.3 ± 3.1 mL O2∙100 mL blood−1, P = 0.031) were lower in the FM group. No significant group differences emerged in ∆$$\dot{\text{V}}$$ V ˙ O2/∆work rate (11.1 vs. 10.8 mL∙min−1∙W−1, P = 0.248) or ∆$$\dot{\text{Q}}$$ Q ˙ /∆$$\dot{\text{V}}$$ V ˙ O2 (6.58 vs. 5.75, P = 0.122) slopes. Conclusions Both $$\dot{\text{Q}}$$ Q ˙ and C(a-v)O2 contribute to lower $$\dot{\text{V}}$$ V ˙ O2peak in FM. The exercise responses were normal and not suggestive of a muscle metabolism pathology. Trial registration ClinicalTrials.gov, NCT03300635. Registered 3 October 2017—Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03300635.