Effect of fibromyalgia on demographic, biochemical, metabolic and inflammatory profiles: a single-centre retrospective study.

OBJECTIVES: The objective of this study is to ascertain the disparities in demographic features and biochemical profiles between individuals diagnosed with fibromyalgia (FM) and a control group of healthy individuals. METHODS: This retrospective, cross-sectional study compared the demographic, biochemical, metabolic, and inflammatory indexes and rates of 174 FM patients diagnosed using the American College of Rheumatology 2016 diagnostic criteria between January 2023 and January 2024, and 186 healthy control groups. RESULTS: There was no difference between the FM and control groups in terms of alcohol consumption, marital status, or diabetes mellitus. The smoking rate is higher, and the educational level was found to be lower for FM versus the control. There was no significant difference between FM and controls regarding waist-height ratio, triglyceride-glucose index, plasma atherogenic index, vitamin B12, and folate levels. Monocyte HDL ratio, cardiometabolic index, magnesium, HbA1c, and ferritin levels were significantly higher in the control than in FM (p<0.001, p=0.039, p=0.007, p<0.001, p<0.001, respectively). C-reactive protein, erythrocyte sedimentation rate, systemic immune-inflammatory index, neutrophil-lymphocyte rate, platelet lymphocyte rate, and vitamin D levels were found to be higher in FM compared to control (p=0.001, p=0.032, p=0.003, p=0.030, p=0.003, p<0.001, respectively). A weak positive correlation was observed between the fibromyalgia impact questionnaire (FIQ) score and disease duration, as well as between pain degree and ESR, and pain degree and CRP. The study revealed a weak inverse relationship between Widespread Pain Index (WPI) and waist circumference. CONCLUSIONS: This study highlights fthe association f ibromyalgia with elevated inflammatory markers, altered metabolic parameters, and specific demographic characteristics.

Proteomics in Patients with Fibromyalgia Syndrome: A Systematic Review of Observational Studies.

PURPOSE OF REVIEW: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies. RECENT FINDINGS: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle-Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). The most important proteins identified involved transferrin, α-, ß-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response.

Exploring levels of TSH and FT4 in patients with chronic fatigue syndrome (CFS), fibromyalgia (FM) and healthy controls did not reveal any associations between fatigue score and level of thyroid hormones.

AIM: The diagnoses of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are highly associated with fatigue and pain, respectively. Physiologically and clinically an effect of thyroid status on fatigue and pain is expected. There may be clinically relevant differences in thyroid hormone axes though within values of reference in both patients with normal thyroid hormones, or in patients with well-regulated thyroid disease. These potential differences are explored in this study. MATERIALS AND METHODS: In the present study, female patients with CFS (n = 49) and FM (n = 58) as well as female healthy controls (n = 53) were included. We explored plasma levels of TSH and FT4 between the groups using Kruskall-Wallis, and the relation between fatigue score and levels of TSH and FT4 by means of Spearman's rho. RESULTS: There were no group differences between CFS patients, FM patients, and healthy controls in levels of TSH and FT4. CONCLUSION: As one might clinically and physiologically expect an association between thyroid function and fatigue, which may be associated with clinical disorders such as CFS and FM, we suggest future studies to examine the field further by exploring the influence of thyroid receptors and responses of the thyroid hormone cascade.

Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.

OBJECTIVES: The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC). METHODS: Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774). RESULTS: Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P = 0.0034; I2 = 71%, Q2P = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P = 0.045; I2 = 39%, Q2P = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P = 0.01; I2 = 61%, Q2P = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P < 0.001; I2 = 10%, Q2P = 0.34) in fibromyalgia patients compared with HC. CONCLUSION: We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.

Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates.

Physiosomatic symptoms are an important part of schizophrenia phenomenology. The aim of this study is to examine the biomarker, neurocognitive and symptomatic correlates of physiosomatic symptoms in schizophrenia. We recruited 115 schizophrenia patients and 43 healthy controls and measured the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) scale, schizophrenia symptom dimensions, and the Brief Assessment of Cognition in Schizophrenia. We measured neuro-immune markers including plasma CCL11 (eotaxin), interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box 1 protein (HMGB1) and endogenous opioid system (EOS) markers including κ-opioid receptor (KOR), µ-opioid receptor (MOR), endomorphin-2 (EM2) and ß-endorphin. Patients with an increased FF score display increased ratings of psychosis, hostility, excitement, formal though disorders, psycho-motor retardation and negative symptoms as compared with patients with lower FF scores. A large part of the variance in the FF score (55.1%) is explained by the regression on digit sequencing task, token motor task, list learning, IL-10, age (all inversely) and IL-6 (positively). Neural network analysis shows that the top-6 predictors of the FF score are (in descending order): IL-6, HMGB1, education, MOR, KOR and IL-10. We found that 45.1% of the variance in a latent vector extracted from cognitive test scores, schizophrenia symptoms and the FF score was explained by HMGB1, MOR, EM2, DKK1, and CCL11. Physiosomatic symptoms are an integral part of the phenome of schizophrenia. Neurotoxic immune pathways and lowered immune regulation coupled with alterations in the EOS appear to drive the physiosomatic symptoms of schizophrenia.

Associations Among Nitric Oxide and Enkephalinases With Fibromyalgia Symptoms.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome of uncertain etiology, characterized by the presence of widespread pain. Both nitric oxide and enkephalinases modulate pain perception. OBJECTIVES: The aim of this study was to evaluate the relationships among serum nitric oxide levels, oxytocinase activity, and enkephalin-degrading aminopeptidase (EDA) activity with pain-related clinical manifestations in women with FM. METHODS: We performed an observational case study in a population of 58 women diagnosed with FM. Serum nitric oxide levels were analyzed by an ozone chemiluminescence-based assay. Both serum oxytocinase and EDA activities were fluorometrically determined. Pain threshold and pain magnitude were evaluated using the PainMatcher. The pressure pain thresholds were measured using a digital pressure algometer. We used a visual analog scale, the Central Sensitization Inventory, the Revised Fibromyalgia Impact Questionnaire, and the Beck Anxiety Inventory to assess the global level of pain, the symptoms associated with the central sensitization syndrome, the severity of FM, and the anxiety level, respectively. RESULTS: Multiple linear regression analysis adjusted by age, body mass index, and menopause status revealed significant associations between nitric oxide levels and dominant occiput pressure pain thresholds, nondominant occiput pressure pain thresholds, and FM effects. Significant associations of oxytocinase activity with the visual analog scale and dominant knee pressure pain thresholds were also found. Moreover, results showed a significant association between high EDA activity levels and dominant second-rib pressure pain thresholds. DISCUSSION: Our data have shown significant relationships of serum nitric oxide levels and oxytocinase and EDA activities with some body pressure pain thresholds, the daily activity level, and the global intensity of pain in women with FM. These results suggest that pain, which is the main symptom of this syndrome, may be related to alterations in nitric oxide levels and in oxytocinase and EDA activities in patients with FM.

Metabolic fingerprinting for diagnosis of fibromyalgia and other rheumatologic disorders.

Diagnosis and treatment of fibromyalgia (FM) remains a challenge owing to the lack of reliable biomarkers. Our objective was to develop a rapid biomarker-based method for diagnosing FM by using vibrational spectroscopy to differentiate patients with FM from those with rheumatoid arthritis (RA), osteoarthritis (OA), or systemic lupus erythematosus (SLE) and to identify metabolites associated with these differences. Blood samples were collected from patients with a diagnosis of FM (n = 50), RA (n = 29), OA (n = 19), or SLE (n = 23). Bloodspot samples were prepared, and spectra collected with portable FT-IR and FT-Raman microspectroscopy and subjected to metabolomics analysis by ultra-HPLC (uHPLC), coupled to a photodiode array (PDA) and tandem MS/MS. Unique IR and Raman spectral signatures were identified by pattern recognition analysis and clustered all study participants into classes (FM, RA, and SLE) with no misclassifications (p < 0.05, and interclass distances > 2.5). Furthermore, the spectra correlated (r = 0.95 and 0.83 for IR and Raman, respectively) with FM pain severity measured with fibromyalgia impact questionnaire revised version (FIQR) assessments. Protein backbones and pyridine-carboxylic acids dominated this discrimination and might serve as biomarkers for syndromes such as FM. uHPLC-PDA-MS/MS provided insights into metabolites significantly differing among the disease groups, not only in molecular m/z+ and m/z- values but also in UV-visible chromatograms. We conclude that vibrational spectroscopy may provide a reliable diagnostic test for differentiating FM from other disorders and for establishing serologic biomarkers of FM-associated pain.

Association between daily level of objective physical activity and C-Reactive protein in a representative national sample of adults with self-reported diagnosed arthritis or fibromyalgia.

PURPOSE: Examine the association between physical activity and sedentary time with high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. We also investigated the dose of physical activity that was associated with lower clinical levels of high sensitivity C-Reactive protein (< 3 mg/L). MATERIALS AND METHODS: Observational design was used to evaluate the variables of interest-based on the Canadian Health Measures Survey cycle 1-3 (2007-2012). Generalized adjusted additive models were used to explore the shape of the association between high sensitivity C-Reactive protein, daily physical activity, step count and sedentary time. High sensitivity C-Reactive protein was measured with blood samples. Physical activity, number of steps and sedentary time were objectively assessed using an Actical accelerometer. RESULTS: Daily moderate to vigorous physical activity and step count were significantly associated with lower high sensitivity C-Reactive protein levels, but daily light physical activity and sedentary time were not associated with high sensitivity C-Reactive protein levels, even after controlling for age, sex, daily smoking, body mass index, household income, level of education levels, marital status, work year and accelerometer wear time and season of accelerometer. Non-linear dose-response patterns were observed between daily moderate to vigorous physical activity as well as step count with high sensitivity C-Reactive protein levels. Lower high sensitivity C-Reactive protein levels were associated with 1-150 min of daily moderate to vigorous physical activity and with daily step count starting at 4000 in people with arthritis. Adults with fibromyalgia had lower levels of high sensitivity C-Reactive protein when engaging in 10-35 min of daily moderate to vigorous physical activity and in 5000-9000 daily steps. Optimal and specific doses of daily moderate to vigorous physical activity and steps were independently related to lower high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. CONCLUSIONS: Daily moderate to vigorous physical activity and step count were associated with high sensitivity C-Reactive protein levels that were below the clinical threshold. Given the positive outcomes of physical activity on health, adults with arthritis and fibromyalgia may benefit from these specific recommendations.

Serum agrin and talin are increased in major depression while agrin and creatine phosphokinase are associated with chronic fatigue and fibromyalgia symptoms in depression.

Chronic fatigue and fibromyalgia symptoms frequently occur in major depressive disorder (MDD). The pathophysiology of these symptoms may in part, be ascribed to activated immune pathways, although it is unclear whether muscular factors play a role in their onset. The aim of the present study is to examine the role of muscle proteins in major depression in association with symptoms of chronic fatigue and fibromyalgia. We measured serum levels of agrin, talin-2, titin, and creatine phosphokinase (CPK) as well as the FibroFatigue (FF), the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory (BDI-II) scores in 60 MDD patients and 30 healthy controls. The results show a significant increase in agrin and talin-2 in MDD patients as compared with controls. There were highly significant correlations between agrin and HAM-D, BDI-II and FF scores. Agrin, but not talin or titin, was significantly and positively associated with all 12 items of the FF scale. We found that a large part of the variance in HAM-D (47.4%), BDI-II (43.4%) and FF (43.5%) scores was explained by the regression on agrin, smoking, female sex (positively associated) and education (inversely associated). CPK was significantly and inversely associated with the total FF score and with muscle and gastro-intestinal symptoms, fatigue, a flu-like malaise, headache and memory, autonomic and sleep disturbances. These results suggest that aberrations in neuromuscular (NMJs) and myotendinous junctions play a role in MDD and that the aberrations in NMJs coupled with lowered CPK may play a role in chronic fatigue and fibromyalgia symptoms in MDD. Moreover, the increase of agrin in MDD probably functions as part of the compensatory immune-regulatory system (CIRS).

Commonalities and differences in abnormal peripheral metabolites between patients with fibromyalgia and complex regional pain syndrome.

Background: Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain that could contribute to multifactorial pathological mechanisms.Methods: We investigated peripheral metabolites in FM and CRPS patients compared to healthy controls based on cross-sectional study.Results: Mean corpuscular hemoglobin (p < 0.001), mean corpuscular volume (p = 0.014), and total bilirubin levels (p = 0.017) were lower in FM patients than in healthy controls. On the other hand, CRPS patients showed lower levels of total bilirubin than healthy controls (p = 0.037). Creatinine level was lower in FM patients (p = 0.057) compared to healthy controls, particularly when comparing the low-hemoglobin subgroup among FM patients (p = 0.035) with the low-hemoglobin subgroup among healthy controls. Red blood cell count (r = -0.620, p = 0.031), hematocrit (r = -0.593, p = 0.042), and creatinine level (r = -0.598, p = 0.040) showed negative correlations with McGill Pain Questionnaire-Affective (MPQ-A) scores in FM patients. A negative correlation was observed between MCV and McGill Pain Questionnaire-Sensory scores (r = -0.680, p = 0.015) in CRPS patients.Conclusion: We found specific peripheral metabolites that may exhibit different tendency between FM and CRPS patients as well as some common metabolites, which may be associated with peripheral pathology in the patients. Considering this study had a few limitations such as a small sample sizes and using a liberal threshold of significance in the correlation analysis, future studies with larger sample sizes may be needed to generalize these findings.

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients.

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-ß and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

Patients with Fibromyalgia and Chronic Fatigue Syndrome show increased hsCRP compared to healthy controls.

Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are both chronic disorders that have a devastating effect on the lives of the affected patients and their families. Both conditions have overlapping clinical features that partly resemble those of inflammatory disorders. The etiology is still not understood, and it is suggested that the immune system might be a contributing factor. So far, the results are inconclusive. The purpose of this study was to compare the two conditions and investigate the level of the inflammatory marker high-sensitivity CRP (hsCRP) in CFS and FM patients compared to healthy controls. Female participants aged 18-60 years were enrolled in this study. The group consisted of 49 CFS patients, 57 FM patients, and 54 healthy controls. hsCRP levels were significantly higher for both the CFS and the FM groups compared to healthy controls when adjusting for age, smoking, and BMI (p < .001). There was no difference between the two patient groups. The level of hsCRP was affected by BMI but not by age and smoking. Patients with CFS and FM have higher concentrations of hsCRP compared to healthy controls. This remains significant even after adjusting for BMI. CFS and FM cannot be distinguished from each other on the basis of hsCRP in our study.

A descriptive pilot study of mitochondrial mutations & clinical phenotype in fibromyalgia syndrome.

BACKGROUND & OBJECTIVES: : Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS. METHODS: : Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at. RESULTS: : None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients. INTERPRETATION & CONCLUSIONS: : Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.

Performance of 2016 revised fibromyalgia diagnostic criteria in patients with rheumatoid arthritis.

Fibromyalgia (FM) is a common comorbidity in rheumatoid arthritis (RA). Recently, there were several updates for the American College of Rheumatology (ACR) FM criteria. To assess the performance of the 2016 revised ACR FM criteria in patients with RA in comparison to 1990 criteria and to study the relation to composite disease measures. This study included 130 adult RA patients fulfilling the 2010 ACR/EULAR classification criteria for RA. Patients were evaluated according to 2016 and 1990 ACR criteria for FM. Kappa agreement between the two criteria was determined. Spearman's correlation between the polysymptomatic distress scale (PSD) and selected variables including disease activity score-28 with erythrocyte sedimentation rate (DAS-28 ESR), clinical disease activity index (CDAI), patient global assessment (PGA), and visual analogue scale (VAS) for pain was evaluated. Of the 130 RA patients, 52 patients (40%) satisfied the 2016 criteria and 40 (31.5%) the 1990 criteria. The Kappa agreement between the two criteria was 0.733. RA patients with FM had higher DAS28-ESR, CDAI, PGA, and VAS compared with those without FM. A significant positive correlation was found between the polysymptomatic Distress scale (PSD) and DAS28-ESR, CDAI, and PGA (rs 0.481, 0.516, 0.511, respectively, P < 0.001). FM coexists in a substantial number of RA patients according to the 2016 revised criteria and associated with high composite disease activity measures. Therefore, assessment of FM should be considered in RA patients with persistently high disease activity.

Association of ferritin levels with depression, anxiety, sleep quality, and physical functioning in patients with fibromyalgia syndrome: a cross-sectional study.

AIM: To determine the frequency of ferritin deficiency in individuals with fibromyalgia syndrome (FMS) and to evaluate the association of ferritin level with depression, anxiety, sleep quality, and physical functioning. METHODS: This cross-sectional study, conducted from 2016 to 2017, compared the frequency of ferritin deficiency between 100 non-anemic fibromyalgia patients and 100 non-anemic individuals without FMS. Serum ferritin level of <30 ng/mL indicated iron deficiency. FMS patients filled out demographic questionnaire, Fibromyalgia Impact Questionnaire, Beck Anxiety Inventory, Beck Depression Inventory, and Pittsburg Sleep Quality Index. RESULTS: Median serum ferritin level was 20.95 ng/mL. A total of 64% of patients and 42% of controls had iron deficiency. Beck Anxiety Inventory, Beck Depression Inventory, and Pittsburgh Sleep Quality Index scores were not associated with ferritin levels. FMS patients with poor sleep quality had significantly higher Beck Depression Inventory, Beck Anxiety Inventory, and Fibromyalgia Impact Questionnaire scores (P<0.05). In individuals with poor sleep quality, lower ferritin levels also correlated with higher Beck Depression Inventory scores (r=-0.277, P<0.05). Sleep quality was not significantly associated with age, body mass index, duration of diagnosis, and serum ferritin levels. CONCLUSIONS: Patients with fibromyalgia syndrome have a rather high prevalence of non-anemic iron deficiency. No associations were found between serum ferritin level and anxiety, depression, sleep quality, and physical functioning.

Machine Learning to Understand the Immune-Inflammatory Pathways in Fibromyalgia.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of FM.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers' effectiveness in axial spondyloarthritis: results of a prospective, multicentre study.

OBJECTIVE: To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) response. DESIGN: Prospective observational study with two visits 3 months apart. PATIENTS: Adult patients with AxSpa initiating a TNFb. STUDY GROUPS: FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM. STATISTICAL ANALYSIS: Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response. RESULTS: Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups. CONCLUSION: This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.

Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and Substance P Levels: A Randomized Sham and Placebo-Controlled Clinical Trial.

Objective: The aim of this study was to evaluate the effects of acupuncture treatment on serum levels of serotonin and substance P (SP) as well as on clinical parameters in patients with fibromyalgia (FM). Methods: This is a randomized controlled clinical trial. Seventy-five women with FM were randomized into one of three kinds of acupuncture treatment: real acupuncture group (AcG), sham acupuncture group (ShG), and simulated acupuncture group (SiG). Treatments were applied semiweekly for four weeks. The serum levels of serotonin and SP were evaluated before and after the eight sessions. Patients were clinically assessed by visual analog scale (VAS), the number of tender points (NTP), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Nottingham Health Profile (NHP) at baseline, after the last treatment, and one and three months after completion of all treatments. Results: Serum serotonin values increased significantly after treatment in AcG and ShG (P < 0.001 and P < 0.01, respectively). The increase in the AcG was also different from both of the other groups (P < 0.01). While SP levels decreased in the AcG, they increased in the SiG (P = 0.001). In the AcG, significant improvements were found in almost all clinical outcomes after treatment. These usually continued for three months. In the ShG, there were also significant changes on the NTP, VAS, FIQ, and BDI scores after treatment. Improvements on the NTP and FIQ scores lasted for three months. In the SiG, significant improvements were found only in the NTP, VAS, and BDI scores after treatment. Conclusions: Acupuncture, rather than sham or placebo acupuncture, may lead to long-term improvements on clinical outcomes and pain neuromediator values. Changes in serum serotonin and SP levels may be a valuable explanation for acupuncture mechanisms in FM treatment.