Ba-Duan-Jin alleviates pain and fibromyalgia-related symptoms in patients with fibromyalgia: results of a randomised controlled trial.

OBJECTIVES: Fibromyalgia is a chronic debilitating pain syndrome. There has been growing interest in the development of non-pharmacological therapies. Ba-Duan-Jin is an ancient Chinese exercise for health promotion, yet easy to learn. The purpose of this study is to evaluate the effectiveness of Ba-Duan-Jin in managing fibromyalgia symptoms experienced by Chinese patients. METHODS: In this randomised, usual therapy-controlled study, patients with fibromyalgia practiced Ba-Duan-Jin for one hour, twice a week for 12 weeks. The primary outcome measure was change in the Visual Analogue Scale for pain (pain VAS). Secondary outcomes included the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Assessment of Fatigue (MAF), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Perceived Stress Scale (PSS), and the Tender Point Count (TPC). These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patient Global Impression of Change (PGIC) was collected at week 12. The Mann-Whitney U-test was performed using the intention-to-treat population. RESULTS: A total of 62 fibromyalgia patients were randomised to the Ba-Duan-Jin or the control groups. For the Ba-Duan-Jin group, significant improvement in pain VAS, FIQ, MAF, PSQI, and TPC were documented at weeks 4 (p≤0.046) and continued at week 8 (p≤0.003). At week 12, all of the outcome measures including BDI and PSS exhibited significant improvement (p≤0.004), and PGIC ratings were significantly better (p<0.001). No significant changes in the control group were observed. CONCLUSIONS: This study suggests that Ba-Duan-Jin exercise has the potential to be a valuable non-pharmacological intervention among Chinese fibromyalgia patients.

2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria.

OBJECTIVES: The provisional criteria of the American College of Rheumatology (ACR) 2010 and the 2011 self-report modification for survey and clinical research are widely used for fibromyalgia diagnosis. To determine the validity, usefulness, potential problems, and modifications required for the criteria, we assessed multiple research reports published in 2010-2016 in order to provide a 2016 update to the criteria. METHODS: We reviewed 14 validation studies that compared 2010/2011 criteria with ACR 1990 classification and clinical criteria, as well as epidemiology, clinical, and databank studies that addressed important criteria-level variables. Based on definitional differences between 1990 and 2010/2011 criteria, we interpreted 85% sensitivity and 90% specificity as excellent agreement. RESULTS: Against 1990 and clinical criteria, the median sensitivity and specificity of the 2010/2011 criteria were 86% and 90%, respectively. The 2010/2011 criteria led to misclassification when applied to regional pain syndromes, but when a modified widespread pain criterion (the "generalized pain criterion") was added misclassification was eliminated. Based on the above data and clinic usage data, we developed a (2016) revision to the 2010/2011 fibromyalgia criteria. Fibromyalgia may now be diagnosed in adults when all of the following criteria are met: CONCLUSIONS: The fibromyalgia criteria have good sensitivity and specificity. This revision combines physician and questionnaire criteria, minimizes misclassification of regional pain disorders, and eliminates the previously confusing recommendation regarding diagnostic exclusions. The physician-based criteria are valid for individual patient diagnosis. The self-report version of the criteria is not valid for clinical diagnosis in individual patients but is valid for research studies. These changes allow the criteria to function as diagnostic criteria, while still being useful for classification.

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells.

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain affecting more women than men. Even though clinical studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or reliable objective markers has hampered development of effective treatments. Here we report that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP), and SP-structurally-related hemokinin-1 (HK-1) were significantly (P = 0.026, P < 0.0001, and P = 0.002, respectively) elevated (0.82 ± 0.57 ng/ml, 0.39 ± 0.18 ng/ml, and 7.98 ± 3.12 ng/ml, respectively) in the serum of patients with FMS compared with healthy controls (0.49 ± 0.26 ng/ml, 0.12 ± 0.1 ng/ml, and 5.71 ± 1.08 ng/ml, respectively). Moreover, SP and HK-1 levels were positively correlated (Pearson r = 0.45, P = 0.002) in FMS. The serum concentrations of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF) were also significantly (P = 0.029 and P = 0.006, respectively) higher (2.97 ± 2.35 pg/ml and 0.92 ± 0.31 pg/ml, respectively) in the FMS group compared with healthy subjects (1.79 ± 0.62 pg/ml and 0.69 ± 0.16 pg/ml, respectively). In contrast, serum IL-31 and IL-33 levels were significantly lower (P = 0.0001 and P = 0.044, respectively) in the FMS patients (849.5 ± 1005 pg/ml and 923.2 ± 1284 pg/ml, respectively) in comparison with healthy controls (1281 ± 806.4 pg/ml and 3149 ± 4073 pg/ml, respectively). FMS serum levels of neurotensin were not different from controls. We had previously shown that CRH and SP stimulate IL-6 and TNF release from mast cells (MCs). Our current results indicate that neuropeptides could stimulate MCs to secrete inflammatory cytokines that contribute importantly to the symptoms of FMS. Treatment directed at preventing the secretion or antagonizing these elevated neuroimmune markers, both centrally and peripherally, may prove to be useful in the management of FMS.

Fibromyalgia syndrome in need of effective treatments.

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

INTRODUCTION: The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. METHODS: This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). RESULTS: Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. CONCLUSIONS: The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00423605.

Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study.

BACKGROUND: Data from an open-label trial suggest that mirtazapine might prove useful in treatment of fibromyalgia syndrome (FMS). OBJECTIVE: To obtain preliminary efficacy data of mirtazapine for estimation of sample size requirements for a Phase 2 clinical trial in FMS. METHODS: This 13-week randomized controlled trial compared the effects of mirtazapine 15 mg/day, mirtazapine 30 mg/day, and placebo in 40 patients with FMS. The primary outcomes were change in Pain Visual Analog Scale (PVAS) and proportion of pain responders (≥30% PVAS reduction). Secondary outcomes included scores from the Jenkins Sleep Scale (JSS), Patient Global Impression of Change (PGIC), Fibromyalgia Impact Questionnaire (FIQ), Hamilton Depression Rating Scale (HAM-D), Patient Global Assessment, and self-reported adverse events. RESULTS: Significant within-group PVAS reductions from baseline were observed in all 3 groups, with the greatest improvement in the mirtazapine 30-mg group (p < 0.005); between-group difference was not significant. The proportion of pain responders did not meet significance criteria (66.67% for mirtazapine 30 mg, 50% for mirtazapine 15 mg, 41.67% for placebo). Significant within-group improvement in JSS scores was seen for mirtazapine 30 mg (p < 0.01) and mirtazapine 15 mg (p < 0.05). Between-group comparison achieved significance for JSS item 3, waking several times per night (p < 0.05). On the PGIC, 72.73% felt better with both mirtazapine dosages compared with 50% for placebo. Within-group FIQ responses indicated improvement in only mirtazapine-treated groups, whereas within-group improvement for HAM-D and Patient Global Assessment was observed in all groups. Based on our findings, the sample size requirement (80% power, 5% type I error) should be 83 per group to detect PVAS change difference between mirtazapine 30 mg and placebo. Common mirtazapine-related adverse events were increased appetite and weight gain. CONCLUSIONS: Patients with FMS taking mirtazapine exhibited within-group significant improvement in most of the measured outcomes. Between-group analysis was predictably compromised by the small sample size. Mirtazapine was well tolerated. Further study with a larger sample size is likely to be useful.

Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: a randomized pilot study.

To evaluate the effects of aerobic training and stretching on serum levels of serotonin (5HT) and its main metabolite 5-hydroxindolacetic acid (5HIAA). Twenty-two women with FM were randomized into one of two exercise modalities (aerobic walking exercise or stretching exercise) to be accomplished three times a week for 20 weeks. The serum levels of 5HT and 5HIAA were evaluated before and after the exercise program by high performance liquid chromatography (HPLC) with colorimetric detection. Within group analysis (pre-post) showed that serum levels of both 5HT and 5HIAA changed significantly in the aerobic group during the 20-week course of therapy (5HT: P = 0,03; 5HIAA: P = 0,003). In the stretching group, however, no statistically significant change was observed (5HT: P=0,491; 5HIAA: P=0,549). Between group statistical comparisons of laboratory measures disclosed that aerobic training was superior to stretching in that it significantly increased the levels of 5HIAA (F test = 6.61; P = 0.01), but the average difference between groups on the levels of 5HT did not meet significance criteria (F test = 3.42; P = 0.08). Aerobic training increases the 5HIAA and 5HT levels and it could explain why aerobic exercise can improve symptoms in fibromyalgia syndrome patient more than stretching exercise.

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. METHODS: A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score (0 to 10 scale) was used to define tiredness subgroups. Patients were stratified into 3 subgroups: mild (0 to 3), moderate (4 to 6), and severe (7 to 10) tiredness. Analysis of covariance models and logistic regressions were used to test treatment-by-tiredness subgroup interactions. RESULTS: Data from the first 3 months are included in this post hoc analysis (duloxetine N = 797, placebo N = 535). At baseline, the distribution of tiredness severity in the duloxetine and placebo groups respectively was 3.64% and 3.75% mild, 16.71% and 15.57% moderate, and 79.65% and 80.68% severe. Rates of clinically significant (≥30% and ≥50%) improvement in brief pain inventory (BPI) average pain were similar across the tiredness subgroups. Tiredness severity at baseline was not negatively associated with the effects of duloxetine on patients' reports of functional ability using the FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression and the medical outcomes study short form-36 (SF-36). CONCLUSIONS: Studies of duloxetine in fibromyalgia have demonstrated clinically significant improvements in pain and functional ability (FIQ, SF-36). This post hoc analysis of data shows that the efficacy of duloxetine among patients with fibromyalgia does not vary as a function of baseline ratings of fatigue/tiredness.