Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia

Introduction  

We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI).     

Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin

Introduction  

The aim of the present study was to determine the brain areas associated with fibromyalgia, and whether pretreatment regional cerebral blood flow (rCBF) can predict response to gabapentin treatment.     

La fibromyalgie est-elle une maladie psychiatrique ?

Epidemiology

The lifetime prevalence of fibromyalgia in France is estimated between 1.4% and 2.2%. The male/female sex ratio is 1:7, and symptoms usually appear between the age of30 and 50 years.

Diagnosis

The diagnosis of fibromyalgia is now a rheumatologic diagnosis, based on symptoms including chronic widespread pain and nonrestorative sleep. As fibromyalgia is a highly comorbid disease, it questions about nosographic identity.

Diagnosing psychiatric comorbidity

It is important for the clinician to look for symptoms of depression that are not traditionally comorbid with fibromyalgia: suicidal ideation, anhedonia, self-blame, eating disorders and psychomotor retardation. An anxiety disorder is often secondary to the onset of symptoms, and can sometimes precede the onset of fibromyalgia syndrome. The vast majority of patients with fibromyalgia have a history of traumatic life events.

Pharmacological treatments

The medical treatment to the fibromyalgia syndrome is not necessarily a drug. Treatment of fibromyalgia is currently not the subject to marketing authorization in France and Europe. Pregabalin, duloxetine and milnacipran received marketing authorization for treatment of fibromyalgia in the US, but none have proven effective in the long term. Fibromyalgia, therefore, requires multidisciplinary support from rheumatologists (who make the diagnosis), general practitioners (who guide and advise patients), medical pain specialists and psychiatrists for the treatment of comorbidities.     

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Introduction  

We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.     

Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity—A Taiwanese Population-Based Cohort Study

Objectives

Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia.

Methods

We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0–729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling.

Results

Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 10³ person-years) and reference subjects (n = 15,162; 9.26 per 10³ person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61–1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43–1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity).

Conclusions

Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia.     

Effect of duloxetine in patients with fibromyalgia: tiredness subgroups

Introduction  

This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia.     

Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate

Introduction  

The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables.     

A randomized,double-blind,multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia

Introduction

Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.

Methods

This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.

Results

A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.

Conclusions

This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.

Trial Registration

ClinicalTrials.gov: NCT00830167     

Improvement in multiple dimensions of fatigue in patients with fibromyalgia treated with duloxetine: secondary analysis of a randomized,placebo-controlled trial

Introduction  

Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia.     

A neuronal death model: overexpression of neuronal intermediate filament protein peripherin in PC12 cells

Background  

Abnormal accumulation of neuronal intermediate filament (IF) is a pathological indicator of some neurodegenerative disorders. However, the underlying neuropathological mechanisms of neuronal IF accumulation remain unclear. A stable clone established from PC12 cells overexpressing a GFP-Peripherin fusion protein (pEGFP-Peripherin) was constructed for determining the pathway involved in neurodegeneration by biochemical, cell biology, and electronic microscopy approaches. In addition, pharmacological approaches to preventing neuronal death were also examined.     

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

Introduction

Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia.

Methods

We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q₁₀ levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.

Results

We found reduced levels of coenzyme Q₁₀, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.

Conclusions

These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.     

Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial

Introduction  

The objective of this study was to investigate the effects of moderate-to-high intensity Nordic walking (NW) on functional capacity and pain in fibromyalgia (FM).     

Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials

Introduction  

The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS.     

The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties

Introduction  

The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia (FM) patients. Over the last 18 years, since the publication of the original FIQ, several deficiencies have become apparent and the cumbersome scoring algorithm has been a barrier to widespread clinical use. The aim of this paper is to describe and validate a revised version of the FIQ: the FIQR.     

Treating patients with fibromyalgia in primary care settings under routine medical practice: a claim database cost and burden of illness study

Introduction  

The objective of this study was to analyze health care and non-health care resource utilization under routine medical practice in a primary care setting claims database and to estimate the incremental average cost per patient per year of fibromyalgia syndrome (FMS) compared with a reference population.     

One hundred years ago: A medical minister in Russia

ObjectivesTo evaluate cardiovascular fitness exercise in people with fibromyalgia.DesignRandomised controlled trial.SettingHospital rheumatology outpatients. Group based classes took place at a “healthy living centre.”Participants132 patients with fibromyalgia.InterventionsPrescribed graded aerobic exercise (active treatment) and relaxation and flexibility (control treatment).ResultsCompared with relaxation exercise led to significantly more participants rating themselves as much or very much better at three months: 24/69 (35%) v 12/67 (18%), P=0.03. Benefits were maintained or improved at one year follow up when fewer participants in the exercise group fulfilled the criteria for fibromyalgia (31/69 v 44/67, P=0.01). People in the exercise group also had greater reductions in tender point counts (4.2 v 2.0, P=0.02) and in scores on the fibromyalgia impact questionnaire (4.0 v 0.6, P=0.07).ConclusionsPrescribed graded aerobic exercise is a simple, cheap, effective, and potentially widely available treatment for fibromyalgia.

What is already known on this topic

Fibromyalgia is common debilitating medically unexplained condition affecting around 1% of the populationCurrent treatments are unsatisfactory and most people remain the same after several years of treatmentExercise as a treatment given by healthcare professionals in highly specialised centres is of some short term benefit

What this study adds

For people with fibromyalgia prescribed graded aerobic exercise is an effective treatment that leads to improvements in self reported health statusPrescribed exercise can be undertaken effectively in the community by personal trainers previously inexperienced in management of people with ill health     

Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle – A Microdialysis Study

Objective

Fibromyalgia 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 Methods

32 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.

Results

The 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.

Conclusion

There 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.     

A meta-analysis of the efficacy of fibromyalgia treatment according to level of care

Introduction  

The aim of this paper was to compare the efficacy of the treatments for fibromyalgia currently available in both primary care and specialised settings.     

Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study

Introduction  

Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first five years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the five-year follow-up period and the modulatory effect of pharmacological treatment.     

Vulnerability to traumatic stress in fibromyalgia patients: 19 month follow-up after the great East Japan disaster

Introduction

The aim of this study was to investigate vulnerability and long-term influence of traumatic stress caused by the Great East Japan Disaster which occurred on March 11, 2011, in patients with fibromyalgia, which is a chronic pain syndrome probably involving central sensitization.

Methods

A total of 60 female patients with fibromyalgia were compared with female patients with rheumatoid arthritis (RA, n = 23) as another chronic pain disease, and with female healthy controls (HC, n = 26) in the observational study. To evaluate responses to traumatic stress, the scores of Impact of Event Scale-Revised (IES-R) were assessed one month after the disaster and every six months until 19 months after the disaster. We also evaluated levels of depression during the study period. To know the score of IES-R of patients with fibromyalgia during usual living, we assessed IES-R in another population of fibromyalgia patients without exposure to a great disaster.

Results

The mean score of IES-R one month after the disaster in the fibromyalgia group (24.6 [SD 18.9]) was significantly higher than that of RA group (13.4 [SD 14.5]) or HC group (9.1 [9.2]) (F = 9.96, p < 0.0001). However, the mean score of IES-R in fibromyalgia patients without exposure to a great disaster was (20.3 [SD 18.7]), which was almost the same value as the fibromyalgia group seven months after the disaster (20.2 [SD 19.5]). Repeated measures analysis of variance showed significant effect of time course in the depression-related symptoms (F = 6.68, P = 0.001), and a post-hoc test revealed that the number of depression-related symptoms one month before the disaster was significantly different from other time points until 19 months after the disaster, respectively.

Conclusions

Although response to acute stress induced by the great earthquake was likely to be settled within seven months after the disaster, depression-related symptoms have been increasing for more than one year after the disaster, despite exclusion of patients with major depression at baseline. This long-lasting worsening of depression-related symptoms may have been in response to chronic stress induced by the fear of radiation due to the nuclear power disaster. These findings suggest that patients with fibromyalgia are vulnerable to chronic stress rather than acute stress.