IntroductionFibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM.MethodsA total of 130 women with FM (age 22–64 years, symptom duration 0–35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants’ self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13–18 months. Between-group and within-group differences were calculated using non-parametric statistics.ResultsSignificant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13–18 months.ConclusionsPerson-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention.Trial registrationClinicalTrials.gov identification number: NCT01226784, Oct 21, 2010.

The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P < 0.041), whereas IL-1β was lower (P < 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P = 0.004), while IL-1β had increased in the relaxation group (P = 0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.

BackgroundFibromyalgia (FM) affects approximately 1–3 % of the general population. Fatigue limits the work ability and social life of patients with FM. A few studies of physical exercise have included measures of fatigue in FM, indicating that exercise can decrease fatigue levels. There is limited knowledge about the effects of resistance exercise on multiple dimensions of fatigue in FM. The present study is a sub-study of a multicenter randomized controlled trial in women with FM. The purpose of the present sub-study was to examine the effects of a person-centered progressive resistance exercise program on multiple dimensions of fatigue in women with FM, and to investigate predictors of the potential change in fatigue.MethodsA total of 130 women with FM (age 22–64 years) were included in this assessor-blinded randomized controlled multicenter trial examining the effects of person-centered progressive resistance exercise compared with an active control group. The intervention was performed twice a week for 15 weeks. Outcomes were five dimensions of fatigue measured with the Multidimensional Fatigue Inventory (MFI-20). Information about background was collected and the women also completed several health-related questionnaires. Multiple linear stepwise regression was used to analyze predictors of change in fatigue in the total population.ResultsA higher improvement was found at the post-treatment examination for change in the resistance exercise group, as compared to change in the active control group in the MFI-20 subscale of physical fatigue (resistance group Δ –1.7, SD 4.3, controls Δ 0.0, SD 2.7, p = 0.013), with an effect size of 0.33. Sleep efficiency was the strongest predictor of change in the MFI-20 subscale general fatigue (beta = −0.54, p = 0.031, R2 = 0.05). Participating in resistance exercise (beta = 1.90, p = 0.010) and working fewer hours per week (beta = 0.84, p = 0.005) were independent significant predictors of change in physical fatigue (R2 = 0.14).ConclusionsPerson-centered progressive resistance exercise improved physical fatigue in women with FM when compared to an active control group.Trial registrationClinicalTrials.gov NCT01226784. Registered 21 October 2010.

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

ObjectiveFibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions.Material and Methods32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0–100) and fatigue Borg’s Rating of Perceived Exertion Scale; 6–20) were assessed before and during the entire microdialysis session.ResultsThe repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P’s < .001). There were no correlations between pain or fatigue and cytokine levels after contractions.ConclusionThere were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia.

BackgroundThis study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON).MethodsTwenty-four female patients with FMS (54 ± 8 years) and 27 female CON (54 ± 9 years) were subjected to intramuscular microdialysis of the most painful vastus lateralis muscle before and after 15 weeks of progressive resistance exercise twice per week. Baseline dialysates were sampled in the resting muscle 140 min after insertion of the microdialysis catheter. The participants then performed repetitive dynamic contractions (knee extension) for 20 min, followed by 60 min rest. Pain intensity was assessed with a 0–100 mm visual analogue scale (VAS), and fatigue was assessed with Borg’s RPE throughout microdialysis. Dialysates were sampled every 20 min and analyzed with Luminex for interleukin (IL)-1β, tumor necrosis factor (TNF) alpha, IL-6, and IL-8.ResultsAt both sessions and for both groups the dynamic contractions increased pain (P < 0.012) and fatigue (P < 0.001). The levels of TNF were lower in the FMS group than the CON group at both sessions (P < 0.05), but none of the other cytokines differed between the groups. IL-6 and IL-8 increased after the dynamic contractions in both groups (P < 0.010), while TNF increased only in CON (P < 0.05) and IL-1β did not change. Overall pain intensity was reduced after the 15 weeks of resistance exercise in FMS (P < 0.05), but there was no changes in fatigue or cytokine levels.ConclusionProgressive resistance exercise for 15 weeks did not affect the interstitial levels of IL-1β, TNF, IL-6, and IL-8 in the vastus lateralis muscle of FMS patients or CON.Trial registrationClinicaltrials.gov NCT01226784, registered 21 October 2010.

BackgroundFibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Women with FM also report disability, in terms of negative consequences on activities of daily living. Our recent randomized controlled trial (RCT) is the first study of resistance exercise to show positive effects on pain disability. The resistance exercise program of our RCT emphasized active involvement of participants in planning and progression of the exercise, using the principles of person-centeredness, to support each participant’s ability to manage the exercise and the progress of it. The aim of this sub-study was to investigate explanatory factors for reduced pain disability in women with FM participating in a 15-week person-centered progressive resistance exercise program.MethodsA total of 67 women with FM were included in this sub-study of an RCT examining the effects of person-centered progressive resistance exercise performed twice a week for 15 weeks. Tests of physical capacity and health-related questionnaires were assessed at baseline and after the intervention period. Multivariable stepwise regression was used to analyze explanatory factors for improvements in pain disability.ResultsReduced pain disability was explained by higher pain disability at baseline together with decreased fear avoidance beliefs about physical activity (R2 = 28, p = 0.005). The improvements in the disability domains of recreation and social activity were explained by decreased fear avoidance beliefs about physical activity together with higher baseline values of each disability domain respectively (R2 = 32, p = 0.025 and R2 = 30, p = 0.017). The improvement in occupational disability was explained by higher baseline values of occupational disability (R2 = 19, p = 0.001).ConclusionThe person-centered resistance exercise intervention, based on principles of self-efficacy, had a positive effect on recreational, social and occupational disability. The reduced pain disability seemed to be mediated by decreased fear avoidance beliefs. Age, symptom duration, pain intensity, and muscle strength at baseline had no explanatory value for reduced pain disability, indicating that the person-centered resistance exercise program has the potential to work for anyone with FM who has interest in physical exercise.The trial was registered on October 21, 2010 with ClinicalTrials.gov identification number: NCT01226784.

Women with fibromyalgia perceive an elevated exertion at work, which is associated with physical work-related factors and factors related to fear and anxiety.