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1.  Fibromyalgia, Systemic Lupus Erythematosus (SLE) and the Evaluation of SLE Activity 
The Journal of rheumatology  2009;36(1):82-88.
To determine if fibromyalgia or fibromyalgianess is increased in SLE compared with non-SLE patients, whether fibromyalgia or fibromyalgianess (the tendency to respond to illness and psychosocial stress with fatigue, widespread pain, general increase in symptoms and similar factors ) biases the Systemic Lupus Erythematosus Activity Questionnaire (SLAQ), and to determine if the SLAQ is overly sensitive to fibromyalgia symptoms.
We developed a 16-item SLE symptom scale (SLESS) modeled on the SLAQ and used that scale to investigate the relation between SLE symptoms and fibromyalgianess in 23,321 rheumatic disease patients. Fibromyalgia was diagnosed by survey fibromyalgia criteria and fibromyalgianess was measured using the Symptom Intensity Scale (SI). As comparison groups, we combined patients with rheumatoid arthritis (RA) and non-inflammatory rheumatic disorders into an “arthritis” group and also utilized a physician-diagnosed group of fibromyalgia patients.
Fibromyalgia was identified in 22.1% of SLE and 17.0% of those with arthritis. The SI scale was minimally increased in SLE. The correlation between SLAQ and SLESS was 0.738. SLESS/SLAQ scale items: Raynaud’s, rash, fever, easy bruising and hair loss were significantly more associated with SLE than fibromyalgia, while the reverse was true for headache, abdominal pain, paresthesias/stroke, fatigue, cognitive problems and muscle pain or weakness. There was no evidence of a disproportionate symptom reporting associated with fibromyalgianess. Self-reported SLE was associated with an increased prevalence of fibromyalgia when unconfirmed by physicians compared to SLE confirmed by physicians.
The prevalence of fibromyalgia in SLE is minimally increased compared with its prevalence in patients with arthritis. Fibromyalgianess does not bias the SLESS and should not bias SLE assessments, including the SLAQ.
PMCID: PMC2944223  PMID: 19004039
Systemic Lupus Erythematosus; Fibromyalgia; Systemic Lupus Erythematosus Activity Questionnaire; SLAQ; SLAM
2.  Disability and quality of life in patients with fibromyalgia 
Patients with fibromyalgia often feel disabled in the performance of daily activities. Psychological factors seem to play a pronounced disabling role in fibromyalgia.
The objectives of the study are: Firstly, to investigate contributing factors for disability in fibromyalgia. Secondly, to study psychological distress in patients with fibromyalgia as compared to other nonspecific pain syndromes. And finally, to explore the impact of fibromyalgia on a patient's quality of life.
In this cross sectional study, explaining factors for disability were studied based on a regression analysis with gender, mental health, physical and social functioning as independent variables. For the assessment of disability in fibromyalgia the FIQ was used. The levels of psychological distress in patients with fibromyalgia, Complex Regional Pain Syndrome (CRPS) and chronic low back pain (CLBP) were compared based on scores on the Symptom Checklist (SCL90). Quality of life of patients with fibromyalgia was compared with scores (SF36) of both patients with fibromyalgia and other health conditions as derived from the literature.
Disability in fibromyalgia seemed best explained by a patients mental health condition (β = -0.360 p = 0.02). The level of psychological distress was higher in patients with fibromyalgia as compared to patients with CRPS or CLBP (p < 0.01). The impact of fibromyalgia on quality of life appeared to be high as compared to the impact of other health conditions.
Patients with fibromyalgia report a considerable impact on their quality of life and their perceived disability level seems influenced by their mental health condition. In comparison with patients with other pain conditions psychological distress is higher.
PMCID: PMC2265693  PMID: 18211701
3.  Fibromyalgia: Presentation and management with a focus on pharmacological treatment 
Fibromyalgia is a condition with widespread muscle pain. Prevalence studies showed that 2% to 7% of the population have fibromyalgia, which affects approximately one million Canadians. Fibromyalgia is most common in women, but it also involves men and children. As with most chronic illnesses, the causes of fibromyalgia are unknown. However, recent research supports underlying abnormalities in the central nervous system, which supports fibromyalgia as a chronic disease state and valid clinical entity. Pain is the primary symptom, often accompanied by overwhelming fatigue, sleep dysfunction and cognitive impairment. In 1990, the American College of Rheumatology developed diagnostic criteria for the diagnosis of fibromyalgia. Lifestyle changes, including pacing of activities and aerobic exercise, are very important in managing fibromyalgia symptoms. Emotional and behavioural therapy can also be helpful. Controlled trials of antidepressants, gabapentinoids, tramadol, zopiclone and sodium oxybate have shown effectiveness in fibromyalgia patients. Pregabalin and duloxetine were recently approved in the United States. Effective management of fibromyalgia is complex and requires a multidisciplinary treatment approach. Response and tolerance of different therapeutic interventions vary from patient to patient. Recent advances in the pathophysiology of fibromyalgia offer hope for new and improved therapies in the management of this disabling condition.
PMCID: PMC2799316  PMID: 19225604
Fatigue; Fibromyalgia; Pain; Treatment
4.  Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease 
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.
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.
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.
These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.
PMCID: PMC2875645  PMID: 20109177
5.  Fibromyalgia: When Distress Becomes (Un)sympathetic Pain 
Pain Research and Treatment  2011;2012:981565.
Fibromyalgia is a painful stress-related disorder. A key issue in fibromyalgia research is to investigate how distress could be converted into pain. The sympathetic nervous system is the main element of the stress response system. In animal models, physical trauma, infection, or distressing noise can induce abnormal connections between the sympathetic nervous system and the nociceptive system. Dorsal root ganglia sodium channels facilitate this type of sympathetic pain. Similar mechanisms may operate in fibromyalgia. Signs of sympathetic hyperactivity have been described in this condition. Genetic factors and/or distressful lifestyle may lead to this state of sympathetic hyperactivity. Trauma and infection are recognized fibromyalgia triggers. Women who suffer from fibromyalgia have catecholamine-evoked pain. Sympathetic dysfunction may also explain nonpain-related fibromyalgia symptoms. In conclusion, in fibromyalgia, distress could be converted into pain through forced hyperactivity of the sympathetic component of the stress response system.
PMCID: PMC3200207  PMID: 22110948
6.  Personality and Fibromyalgia Syndrome 
We aimed to review how personality characteristics contribute to the onset, maintenance or modulation of fibromyalgia.
The databases Medline and PsychINFO were examined from 1967 to 2012 to identify studies that investigated associations between fibromyalgia and personality. Search terms included fibromyalgia and personality, trait psychology, characteristics and individual differences.
Numerous studies indicate that patients with fibromyalgia experience psychological distress. Various instruments have been used to evaluate distress and related psychological domains, such as anxiety or depression, in fibromyalgia. In many cases, these same instruments have been used to study personality characteristics in fibromyalgia with a subsequent blurring of cause and effect between personality and psychological distress. In addition, the symptoms of fibromyalgia may change pre-illness personality characteristics themselves. These issues make it difficult to identify specific personality characteristics that might influence the fibromyalgia process. Despite this inherent problem with the methodologies used in the studies that make up this literature review, or perhaps because of it, we found no defined personality profile specific to fibromyalgia. However, many patients with fibromyalgia do show personality characteristics that facilitate psychological responses to stressful situations, such as catastrophising or poor coping techniques, and these in turn associate with mechanisms contributing to fibromyalgia.
No specific fibromyalgia personality is defined but it is proposed that personality is an important filter that modulates a person’s response to psychological stressors. Certain personalities may facilitate translation of these stressors to physiological responses driving the fibromyalgia mechanism.
PMCID: PMC3447191  PMID: 23002409
Fibromyalgia; personality; stress; psychology; instruments.
7.  Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure☆ 
NeuroImage : Clinical  2013;3:163-170.
Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis.
Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices.
Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control.
•Fibromyalgia syndrome patients exhibited shape alterations in the brainstem.•The mean brainstem volume was also significantly reduced in FMS patients.•This volume reduction correlated with clinical manual tender point scores.•Structural alterations in the brainstem may contribute to clinical symptoms of FMS.
PMCID: PMC3791285  PMID: 24179860
8.  Prevalence of Fibromyalgia: A Population-Based Study in Olmsted County, Minnesota, Utilizing the Rochester Epidemiology Project 
Arthritis care & research  2013;65(5):786-792.
Our objective was to estimate and compare the prevalence of fibromyalgia by two different methods, in Olmsted County, Minnesota.
The first method was a retrospective review of medical records of potential cases of fibromyalgia in Olmsted County using Rochester Epidemiology Project (from January 1, 2005, to December 31, 2009) to estimate the prevalence of diagnosed fibromyalgia in clinical practice. The second method was a random survey of adults in Olmsted County using the fibromyalgia research survey criteria to estimate the percentage of responders who met fibromyalgia research survey criteria.
Of the 3,410 potential patients identified by the first method, 1,115 had a fibromyalgia diagnosis documented in the medical record by a health care provider. The age- and sex-adjusted prevalence of diagnosed fibromyalgia by this method was 1.1%. By the second method, of the 2,994 people who received the survey by mail, 830 (27.6%) responded and 44 (5.3%) met fibromyalgia research survey criteria. The age- and sex-adjusted prevalence of fibromyalgia in the general population of Olmsted County by this method was estimated at 6.4%.
To the best of our knowledge, this is the first report of the rate at which fibromyalgia is being diagnosed in a community. This is also the first report of prevalence as assessed by the fibromyalgia research survey criteria. Our results suggest that patients, particularly men, who meet the fibromyalgia research survey criteria are unlikely to have been given a diagnosis of fibromyalgia.
PMCID: PMC3935235  PMID: 23203795
Fibromyalgia; gender; population studies
9.  Brief, Self-Report Fibromyalgia Screener Evaluated in a Sample of Chronic Pain Patients 
Pain medicine (Malden, Mass.)  2013;14(5):730-735.
To validate a self-report fibromyalgia screener in a chronic pain population.
Adults with chronic pain were evaluated with a 6-item, self-report fibromyalgia screening tool, based on revised American College of Rheumatology (ACR) fibromyalgia diagnostic criteria, with fibromyalgia diagnosed when patients experienced chronic pain and scored ≥13 on the ACR Fibromyalgia Symptom severity scale. Patients were independently assigned clinical diagnoses by treating clinicians.
University-based, tertiary care pain clinic
337 mixed chronic pain patients
Agreement between the clinical diagnosis and screener diagnosis was good (P<0.001), with 76% sensitivity and 82% specificity.
A self-administered, brief fibromyalgia screening questionnaire can effectively identify chronic pain patients who will likely have clinical fibromyalgia.
PMCID: PMC3663923  PMID: 23578002
chronic pain; fibromyalgia; screening tool; self report
10.  A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing 
Annals of the Rheumatic Diseases  2004;63(4):450-452.
Objective: To compare the prevalence and test results for bacterial overgrowth between IBS and fibromyalgia.
Methods: Subjects with independent fibromyalgia and IBS were compared with controls in a double blind study. Participants completed a questionnaire, and a lactulose hydrogen breath test was used to determine the presence of SIBO. The prevalence of an abnormal breath test was compared between study participants. Hydrogen production on the breath test was compared between subjects with IBS and fibromyalgia. The somatic pain visual analogue score of subjects with fibromyalgia was compared with their degree of hydrogen production.
Results: 3/15 (20%) controls had an abnormal breath test compared with 93/111 (84%) subjects with IBS (p<0.01) and 42/42 (100%) with fibromyalgia (p<0.0001 v controls, p<0.05 v IBS). Subjects with fibromyalgia had higher hydrogen profiles (p<0.01), peak hydrogen (p<0.0001), and area under the curve (p<0.01) than subjects with IBS. This was not dependent on the higher prevalence of an abnormal breath test. The degree of somatic pain in fibromyalgia correlated significantly with the hydrogen level seen on the breath test (r = 0.42, p<0.01).
Conclusions: An abnormal lactulose breath test is more common in fibromyalgia than IBS. In contrast with IBS, the degree of abnormality on breath test is greater in subjects with fibromyalgia and correlates with somatic pain.
PMCID: PMC1754959  PMID: 15020342
11.  Patient Perspectives on the Impact of Fibromyalgia 
Patient education and counseling  2008;73(1):114-120.
The objective of this study was to elicit and assess important symptom domains and the impact of fibromyalgia on patients’ quality of life and functioning from a patient’s perspective. The intention was to collect this information as part of an overall effort to overcome shortcomings of existing outcome measures in fibromyalgia.
This was a qualitative study in which six focus group sessions with 48 women diagnosed with fibromyalgia were conducted to elicit concepts and ideas to assess the impact of fibromyalgia on their lives.
The focus groups conducted with fibromyalgia patients identified symptom domains that had the greatest impact on their quality of life including pain, sleep disturbance, fatigue depression, anxiety, and cognitive impairment. Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported disrupted relationships with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in careers or education.
The findings from the focus groups revealed that fibromyalgia has a substantial negative impact on patients’ lives.
Practice Implications
A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgia patients.
PMCID: PMC2564867  PMID: 18640807
fibromyalgia; patient focus group; symptom domains; quality of life
12.  Pathophysiology of Fibromyalgia 
The American journal of medicine  2009;122(12 Suppl):S22.
This article reviews the biologic, genetic, and environmental factors that may contribute to the pathophysiology of fibromyalgia. As an affective spectrum disorder, fibromyalgia may share these causal factors with a number of related and co-occurring pain conditions such as irritable bowel syndrome or temporomandibular disorder. There is strong evidence that cardinal pain symptoms of fibromyalgia may be due to alterations in central processing of sensory input, along with aberrations in the endogenous inhibition of pain, Genetic research has shown familial aggregation of fibromyalgia and other related disorders such as major depressive disorder. Exposure to physical or psychosocial stressors, as well as abnormal biologic responses in the autonomic nervous system and neuroendocrine responses, may also contribute to dysfunctional pain processing. As fibromyalgia research continues to progress, it is expected that the pathophysiology of this disorder will be further elucidated, leading to more rational and targeted strategies for the treatment of fibromyalgia patients.
PMCID: PMC2821819  PMID: 19962493
Fibromyalgia; affective spectrum disorders; pathophysiology; neuroendocrine system; autonomic nervous system; genetics; environmental stressors
13.  Dysfunctional Neurotransmitter Systems in Fibromyalgia, Their Role in Central Stress Circuitry and Pharmacological Actions on These Systems 
Pain Research and Treatment  2011;2012:741746.
Fibromyalgia is considered a stress-related disorder, and hypo- as well as hyperactive stress systems (sympathetic nervous system and hypothalamic-pituitary-adrenal axis) have been found. Some observations raise doubts on the view that alterations in these stress systems are solely responsible for fibromyalgia symptoms. Cumulative evidence points at dysfunctional transmitter systems that may underlie the major symptoms of the condition. In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. Since both transmitter and stress systems change during chronic stress, it is conceivable that both systems change in parallel, interact, and contribute to the phenotype of fibromyalgia. As we outline in this paper, subgroups of patients might exhibit varying degrees and types of transmitter dysfunction, explaining differences in symptomatoloy and contributing to the heterogeneity of fibromyalgia. The finding that not all fibromyalgia patients respond to the same medications, targeting dysfunctional transmitter systems, further supports this hypothesis.
PMCID: PMC3195783  PMID: 22110944
14.  Fibromyalgia and Depression 
Pain Research and Treatment  2011;2012:486590.
Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromyalgia and depression and include laboratory findings on the role of depression in fibromyalgia. Further, we comment on several aspects of fibromyalgia which support the development of reactive depression, substantially more so than in other chronic pain syndromes. However, while sharing many features with depression, fibromyalgia is associated with somatic comorbidities and absolutely defined by fluctuating spontaneous widespread pain. Fibromyalgia may, therefore, be more appropriately grouped together with other functional pain disorders, while psychologically distressed subgroups grouped additionally or solely with affective spectrum disorders.
PMCID: PMC3236322  PMID: 22191023
15.  Fibromyalgia: A Primer for the Anesthesia Community 
Purpose of the Review
The present review is intended to give an overview of fibromyalgia for the anesthesiologist. While the basics of the treatment of fibromyalgia are included, the intent is to provide context to discuss the potential implications in perioperative management.
Recent Findings
One of the most important changes in the last year is the new criteria established by the American College of Rheumatology for the diagnosis of fibromyalgia. Instead of a combination of self-report and a tender point examination, there is a new self-report questionnaire that is now used diagnose fibromyalgia. This tool incorporates aspects of widespread body pain and some of the known comorbid symptoms. A score of 0-31 is given, which allows for the disease to be viewed as a continuum of sensitivity and symptomatology, instead of as a binary diagnosis. This continuum has been termed “fibromyalgia-ness.” This article also reviews the advances in understanding of the pathophysiology and emerging therapies. Little is known about the impact of fibromyalgia in the perioperative period.
The impact of fibromyalgia on anesthesia care is not known. Years of quality research have clearly demonstrated multiple pathophysiologic changes that could impact anesthesia care and future study is needed.
PMCID: PMC3422621  PMID: 21799404
fibromyalgia; treatment; anesthesiology; postoperative pain; chronic post-surgical pain
16.  Correlates of Perceived Pain-Related Restrictions among Women with Fibromyalgia 
Pain medicine (Malden, Mass.)  2010;11(11):1698-1706.
To identify correlates of perceived pain-related restrictions in a community sample of women with fibromyalgia.
The fibromyalgia group was composed of white women with a self-reported, physician-given fibromyalgia diagnosis (N = 238) from the Biopsychosocial Religion and Health Study (BRHS). BRHS respondents had participated in the larger Adventist Health Study-2. To identify associations with pain-related restrictions, we used hierarchical linear regression. The outcome measure was subjects' pain-related restrictions (one SF-12 version 2 item). Predictors included age, education, body mass index (BMI), sleep apnea, and fibromyalgia treatment in the last year, as well as standardized measures for trauma, major life stress, depression, and hostility. To better interpret the findings, pain-related restrictions also were predicted in women with osteoarthritis and no fibromyalgia.
Women with fibromyalgia reporting the more severe pain-related restrictions were those who had experienced trauma accompanied by physical pain, were older, less educated, more depressed, more hostile, had high BMI scores, and had been treated for fibromyalgia in the last 12 months (adjusted R2 = 0.308). Predictors in women with osteoarthritis were age, BMI, treatment in the last 12 months, experience of a major life stressor, and greater depression symptom severity (adjusted R2 = 0.192).
In both groups, age, BMI, treatment in the last 12 months, and depression predicted pain-related restrictions. Experience of a traumatic event with physical pain was the strongest predictor in the fibromyalgia group. These findings may be useful in constructing novel treatments and prevention strategies for pain-related morbidity in fibromyalgia patients.
PMCID: PMC3539411  PMID: 21044260
Fibromyalgia; Osteoarthritis; Pain; Central Nervous System; Trauma; Stress
17.  A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia 
Arthritis Research & Therapy  2012;14(5):R217.
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.
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.
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.
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 NCT00830167
PMCID: PMC3580529  PMID: 23062189
18.  Music as a sleep aid in fibromyalgia 
Fatigue and nonrestorative sleep are some of the most common symptoms associated with fibromyalgia, and are associated with a considerable reduction in quality of life. Certain pharmacological agents that positively affect sleep have been shown to improve fibromyalgia symptoms. Delta-embedded music may help to decrease sleep onset latency and, thus, improve sleep. Accordingly, the authors of this study aimed to elucidate the effects that this type of music has on sleep and fibromyalgia symptoms in a cohort of 20 individuals with fibromyalgia.
Interventions to improve sleep in fibromyalgia may generalize to improvements in multiple symptom domains. Delta-embedded music, pulsating regularly within the 0.25 Hz to 4 Hz frequency band of brain wave activity, has the potential to induce sleep.
To assess the effects of a delta-embedded music program over four weeks for sleep induction in patients with fibromyalgia.
The present unblinded, investigator-led pilot study used a within-subject design. Analysis was based on 20 individuals with fibromyalgia who completed the study, of the 24 recruited into the study. The primary outcome variables were the change from baseline in Fibromyalgia Impact Questionnaire (FIQ) and Jenkins Sleep Scale scores. A patient global impression of change was measured on a seven-point Likert scale. Secondary outcome measures, comprised of items 5, 6 and 7 of the FIQ, were used as indicators of pain, tiredness and being tired on awakening.
The FIQ median score of 76.4 (95% CI 61.3 to 82.1) at baseline improved to 60.3 (95% CI 53.1 to 72.0; P=0.004). The Jenkins Sleep Scale median value of 17.5 (95% CI 15.5 to 18.5) at baseline fell to 12.5 (95% CI 8.5 to 14.5; P=0.001) at study completion. The outcomes of the patient global impression of change ratings were mostly positive (P=0.001). Being tired on awakening declined significantly from a median of 9.0 (95% CI 8.0 to 10.0) to 8.0 (95% CI 5.5 to 9.0; P=0.021). However, there was no significant improvement in pain level (baseline median 7.5 [95% CI 7.0 to 8.5] versus study completion median 7.0 [95% CI 6.5 to 8.0]; P=0.335) or tiredness (baseline median 9.0 [95% CI 8.0 to 9.5] versus study completion median 8.0 [95% CI 6.0 to 8.5]; P=0.061). There were no serious adverse events.
Delta-embedded music is a potential alternative therapy for fibromyalgia.
PMCID: PMC4028660  PMID: 24555178
Delta embedded music; Fibromyalgia; Sleep disorders
19.  Factors explaining variance in perceived pain in women with fibromyalgia 
We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain.
Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge.
Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain.
Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.
PMCID: PMC113754  PMID: 12019032
20.  Lack of association between fibromyalgia and sleep apnoea syndrome. 
Annals of the Rheumatic Diseases  1992;51(1):108-111.
To determine whether sleep disorders can cause a fibromyalgia syndrome, 30 patients with sleep apnoea syndrome were studied. All presented an important reduction in deep sleep stages (-93.1 (SD 17.9)% of stage IV and -77.2 (45.7)% of stage III) and frequent episodes of wakening ('arousals'), factors which are involved in fibromyalgia. One patient (3%) met the criteria for fibromyalgia; the estimated prevalence of fibromyalgia for patients attending a general medical clinic is 6%. No significant correlation was found between the number of points which were tender upon pressure and the various sleep parameters studied. It is concluded that sleep disorders alone are not able to produce a fibromyalgia syndrome.
PMCID: PMC1004631  PMID: 1540013
21.  Joint hypermobility and fibromyalgia in schoolchildren. 
Annals of the Rheumatic Diseases  1993;52(7):494-496.
OBJECTIVES--To test the hypothesis that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia, schoolchildren were examined for the coexistence of joint hypermobility and fibromyalgia. METHODS--The study group consisted of 338 children (179 boys, 159 girls; mean age 11.5 years, range 9-15 years) from one public school in Beer-Sheva, Israel. In the assessment of joint hypermobility, the criteria devised by Carter and Bird were used. Any child who met at least three of five criteria was considered to have joint hypermobility. Children were considered to have fibromyalgia if they fulfilled the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia, namely, widespread pain in combination with tenderness of 11 or more of the 18 specific tender point sites. The blind assessments of joint hypermobility (by AG) and fibromyalgia (by DB) were carried out independently. RESULTS--Of the 338 children 43 (13%) were found to have joint hypermobility and 21 (6%) fibromyalgia; 17 (81%) of the 21 with fibromyalgia had joint hypermobility and 17 (40%) of the 43 with joint hypermobility had fibromyalgia. Using chi 2 statistical analysis, joint hypermobility and fibromyalgia were found to be highly associated. CONCLUSIONS--This study suggests that there is a strong association between joint hypermobility and fibromyalgia in schoolchildren. It is possible that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia. More studies are needed to establish the clinical significance of this observation.
PMCID: PMC1005086  PMID: 8346976
22.  Newer treatments for fibromyalgia syndrome 
Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient’s global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia.
PMCID: PMC2643113  PMID: 19337439
fibromyalgia; pain; pharmacological; treatment
23.  Treatment of cervical myelopathy in patients with the fibromyalgia syndrome: outcomes and implications 
European Spine Journal  2007;16(9):1423-1433.
Some patients with fibromyalgia also exhibit the neurological signs of cervical myelopathy. We sought to determine if treatment of cervical myelopathy in patients with fibromyalgia improves the symptoms of fibromyalgia and the patients’ quality of life. A non-randomized, prospective, case control study comparing the outcome of surgical (n = 40) versus non-surgical (n = 31) treatment of cervical myelopathy in patients with fibromyalgia was conducted. Outcomes were compared using SF-36, screening test for somatization, HADS, MMPI-2 scale 1 (Hypochondriasis), and self reported severity of symptoms 1 year after treatment. There was no significant difference in initial clinical presentation or demographic characteristics between the patients treated by surgical decompression and those treated by non-surgical means. There was a striking and statistically significant improvement in all symptoms attributed to the fibromyalgia syndrome in the surgical patients but not in the non-surgical patients at 1 year following the treatment of cervical myelopathy (P ≤ 0.018–0.001, Chi-square or Fisher’s exact test). At the 1 year follow-up, there was a statistically significant improvement in both physical and mental quality of life as measured by the SF-36 score for the surgical group as compared to the non-surgical group (Repeated Measures ANOVA P < 0.01). There was a statistically significant improvement in the scores from Scale 1 of the MMPI-2 and the screening test for somatization disorder, and the anxiety and depression scores exclusively in the surgical patients (Wilcoxon signed rank, P < 0.001). The surgical treatment of cervical myelopathy due to spinal cord or caudal brainstem compression in patients carrying the diagnosis of fibromyalgia can result in a significant improvement in a wide array of symptoms usually attributed to fibromyalgia with attendant measurable improvements in the quality of life. We recommend detailed neurological and neuroradiological evaluation of patients with fibromyalgia in order to exclude compressive cervical myelopathy, a potentially treatable condition.
PMCID: PMC2200733  PMID: 17426987
Cervical myelopathy; Fibromyalgia; Surgery; Treatment outcome; Case control study
24.  Increased absence due to sickness among employees with fibromyalgia 
Little is known about the effect of fibromyalgia on absence due to sickness in working populations.
To examine the risk of absence due to sickness among employees with fibromyalgia.
A prospective cohort study with 1‐year follow‐up of recorded and certified absence due to sickness after a survey of chronic diseases among 34 100 Finnish public sector employees (27 360 women and 6740 men) aged 17–65 years at baseline in 2000–2.
20 224 days of absence due to sickness for the 644 employees with fibromyalgia and 454 816 days for others were documented. Of those with fibromyalgia, 67% had co‐occurring chronic conditions such as osteoarthritis, rheumatoid arthritis, depression or other psychiatric disorders. Compared with employees with none of these chronic conditions, the hazard ratio (HR) adjusted for age, sex and occupational status was 1.85‐fold (95% confidence interval (CI) 1.53 to 2.18) for people with fibromyalgia alone and 2.63‐fold (95% CI 2.34 to 2.96) for employees with fibromyalgia with coexisting conditions. The excess rate of absence due to sickness was 61 episodes/100 person‐years among people with fibromyalgia alone. Among employees with musculoskeletal and psychiatric disorders, secondary fibromyalgia was associated with a 1.4–1.5‐fold increase in risk of absence.
Fibromyalgia is associated with a substantially increased risk of medically certified absence due to sickness that is not accounted for by coexisting osteoarthritis, rheumatoid arthritis or psychiatric disorders.
PMCID: PMC1798407  PMID: 16793839
25.  Oxidative Stress in Fibromyalgia and its Relationship to Symptoms 
Clinical rheumatology  2008;28(4):435-438.
Oxidative stress is thought to play a role in the pathogenesis of fibromyalgia. We examined the hypothesis that oxidative stress was increased in patients with fibromyalgia and related to the severity of symptoms.
Urinary F2 isoprostane excretion was measured in 48 patients with fibromyalgia and compared to those of 96 control subjects. In patients, we examined the association between oxidative stress and symptoms.
Patients with fibromyalgia were significantly more symptomatic than control subjects, but urinary F2 isoprostane excretion did not differ significantly (2.3±1.9 vs 2.8±2.2 ng/mg creatinine) (p=0.16). In patients with fibromyalgia, F2-isoprostane excretion was associated with fatigue VAS (rho=0.30, p=0.04) but not with pain, quality of life, functional capacity, depression, number of tender points or overall impact of fibromyalgia.
oxidative stress is not increased in patients with fibromyalgia, but as was previously found in patients with systemic lupus erythematosus (SLE), oxidative stress was associated with fatigue.
PMCID: PMC2654204  PMID: 19089486
fibromyalgia; oxidative stress; fatigue; F2 isoprostanes

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