The effect of eye movement desensitization and reprocessing on fibromyalgia: A multiple-baseline experimental case study across ten participants.

Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and stiffness in muscles and joints. Traumatic life experiences and post-traumatic stress symptoms play a role in its development and persistence. Although previous research suggests that pain and FM symptoms decrease after eye movement desensitization and reprocessing (EMDR) therapy, its effectiveness has not been investigated in a controlled manner. The present study investigated the effectiveness of a six-session, 90-minute EMDR therapy using a multiple baseline single-case experimental design (SCED) across ten adult females with FM. The SCED involved a baseline, intervention, one- and three-month follow-up phase. The primary outcome was pain. Secondary outcomes included post-traumatic stress symptoms, other FM symptoms (fatigue, stiffness in muscles and joints), and the impact of FM on daily activities and sleep. Data were statistically analyzed by primarily testing means across phases on an individual and group level. Post-traumatic stress symptoms improved significantly in seven participants. Pain severity decreased significantly in six participants, with three of them maintaining significant improvement three months later. One participant showed clinically relevant change one month later. Furthermore, improvements were observed in secondary outcome measures. The findings support the efficacy of EMDR in reducing FM symptoms.

Non-invasive brain stimulation for fibromyalgia: current trends and future perspectives.

Fibromyalgia, a common and enduring pain disorder, ranks as the second most prevalent rheumatic disease after osteoarthritis. Recent years have witnessed successful treatment using non-invasive brain stimulation. Transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsion therapy have shown promise in treating chronic pain. This article reviews the literature concerning non-invasive stimulation for fibromyalgia treatment, its mechanisms, and establishes a scientific basis for rehabilitation, and discusses the future directions for research and development prospects of these techniques are discussed.

MicroRNA-Related Polymorphism and Their Association with Fibromyalgia.

MicroRNAs are tissue-specific expressed short RNAs that serve post-transcriptional gene regulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions, and in the 3'UTR of protein-coding genes. To identify disease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48,329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. Results show that 29 markers had p-values < 1 × 10-3, and the strongest association was observed for rs758459 (p-value of 0.0001), located in the Neurogenin 1 gene which is targeted by hsa-miR-130a-3p. Furthermore, variant rs2295963 is predicted to affect binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fibromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.

Methylation factors as biomarkers of fibromyalgia.

Background: Fibromyalgia (FM) is a common and intractable chronic musculoskeletal pain syndrome, but its exact underlying mechanisms are unknown. This study sought to identify biomarkers of FM and the underlying molecular mechanisms of the disease. Methods: FM-related gene expression profiles (GSE67311) and methylation profiles (GSE85506) were obtained from the Gene Expression Omnibus database, and a differential expression analysis was performed to identify the methylation factors. Subsequently, an enrichment analysis and gene set enrichment analysis (GSEA) were conducted to examine the methylation factors. In addition, the transcriptional regulators of the methylation factors were predicted, and key methylation factors were identified by a receiver operating characteristic curve analysis and nomogram models. Finally, the relationship between FM and cell death (pyroptosis, necroptosis, and cuproptosis) was assessed by a GSEA and gene set variation analysis. Results: A total of 455 methylation factors were identified. The enrichment analysis and GSEA results showed that methylation factors were clearly involved in the biological functions and signaling pathways related to neural, immune inflammation, and pain responses. The transcriptional regulator specificity protein 1 (SP1) may have a broad regulatory role. Finally, seven key methylation factors were identified, of which amino beta (A4) precursor protein binding family B member 2 (APBB2), A-kinase anchor protein 12 (AKAP12), and cluster of differentiation 38 (CD38) had strong clinical diagnostic power. In addition, AKAP12 and CD38 were significantly and negatively associated with sepsis, necrotizing sepsis, and cupular sepsis. Conclusions: Our study suggests that FM is associated with deoxyribonucleic acid methylation. The methylation factors APBB2, AKAP12, and CD38 may be potential biomarkers and should be further examined to provide a new biological framework of the possible disease mechanisms underlying FM.

A retrospective analysis of the prevalence and impact of associated comorbidities on fibromyalgia outcomes in a tertiary care center.

Background: This retrospective study was designed to analyze the prevalence and impact of associated comorbidities on fibromyalgia (FM) outcomes (functionality, pain, depression levels) for patients who participated in an intensive multicomponent clinical program in a tertiary care center. Methods: Participants included a sample of 411 patients diagnosed with FM at a large tertiary medical center using the 2016 ACR criteria. Patients completed an intensive 2-day cognitive behavioral treatment (CBT) program, filled out the Fibromyalgia Impact Questionnaire Revised (FIQR), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pain Catastrophizing Scale (PCS), and were followed for 6 months after treatment completion. T-tests were performed to analyze differences between the presence or absence of select comorbidities for the three outcomes at follow-up. Statistically significant comorbidities (p < 0.05) were used as predictors in multivariable logistic regression models. Results: The FM associated comorbidities in this cohort that had significant impact on the measured outcome domains after treatment program completed were Obesity (FIQR p = 0.024), Hypothyroidism (CES-D p = 0.023, PCS p = 0.035), Gastroesophageal reflux disease GERD (PCS p < 0.001), Osteoarthritis (CES-D p = 0.047). Interestingly, Headache, the most frequent FM associated comorbidity in this cohort (33.6%), did not have a significant impact on the outcome domains at follow-up. Obesity (18.2%) was the only FM associated comorbidity significantly impacting all three outcome domains at follow-up. Conclusion: The present study suggests that addressing obesity may significantly impact outcomes in FM patients.

The role of mind body interventions in the treatment of irritable bowel syndrome and fibromyalgia.

Introduction: Irritable bowel syndrome and fibromyalgia share similar pathophysiologic mechanisms including sensitization of peripheral and central pain pathways, autonomic dysfunction and are often co-diagnosed. Co-diagnosed patients experience increased symptom severity, mental health comorbidities, and decreased quality of life. The role of mind-body interventions, which have significant effects on central pain syndromes and autonomic dysregulation, have not been well-described in co-diagnosed patients. The aim of this state-of-the art narrative review is to explore the relationship between irritable bowel syndrome and fibromyalgia, and to evaluate the current evidence and mechanism of action of mind-body therapies in these two conditions. Methods: The PubMed database was searched without date restrictions for articles published in English using the following keywords: fibromyalgia, irritable bowel syndrome, mind-body interventions, cognitive behavioral therapy, mindfulness based stress reduction, and yoga. Results: Mind-body interventions resulted in improved patient-reported outcomes, and are effective for irritable bowel syndrome and fibromyalgia individually. Specifically, cognitive behavioral therapy and yoga trials showed decreased symptom severity, improved mental health, sleep and quality of life for both conditions individually, while yoga trials demonstrated similar benefits with improvements in both physical outcomes (gastrointestinal symptoms, pain/tenderness scores, insomnia, and physical functioning), mental health outcomes (anxiety, depression, gastrointestinal-specific anxiety, and catastrophizing), and quality of life, possibly due to alterations in autonomic activity. Conclusion: Mind-body interventions especially CBT and yoga improve patient-reported outcomes in both irritable bowel syndrome and fibromyalgia individually. However, limited available data in co-diagnosed patients warrant high quality trials to better tailor programs to patient needs.

The Reliability and Agreement of the Fibromyalgia Survey Questionnaire in an Italian Sample of Obese Patients.

The Fibromyalgia Survey Questionnaire (FSQ) was self-administered by a sample of 207 Italian individuals with obesity to screen for fibromyalgia (FM). We aimed to investigate the inter-rater reliability and the agreement in the detection of FM symptomatology between the self-administered FSQ and the clinical interview conducted by a rheumatologist. All the patients were divided randomly into two groups (group A and group B): a rheumatologist first interviewed patients of group A and after 48 h, the patients completed the self-report FSQ. Patients of group B first completed the FSQ and 48 h later were interviewed by a rheumatologist. The agreement between the measurements was good with the Bland-Altman analysis showing low bias scores for the two subscales of the FSQ. Results showed that 33% of the sample satisfied the criteria for a diagnosis of fibromyalgia. The FSQ is a self-reporting measure that showed substantial reliability providing fast screening for FM symptomatology.

Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments.

Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy, it is of concern that biomarker miRNAs are masked by drug interactions. Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR, and repoDB, we found a list of commonly prescribed drugs that impact FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline a patient's response to treatment and toxicity. Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes, finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic.

Brain Modulation by Electric Currents in Fibromyalgia: A Structured Review on Non-invasive Approach With Transcranial Electrical Stimulation.

Fibromyalgia syndrome (FMS) is a complex disorder where widespread musculoskeletal pain is associated with many heterogenous symptoms ranging from affective disturbances to cognitive dysfunction and central fatigue. FMS is currently underdiagnosed and often very poorly responsive to pharmacological treatment. Pathophysiology of the disease remains still obscure even if in the last years fine structural and functional cerebral abnormalities have been identified, principally by neurophysiological and imaging studies delineating disfunctions in pain perception, processing and control systems. On such basis, recently, neurostimulation of brain areas involved in mechanism of pain processing and control (primary motor cortex: M1 and dorsolateral prefrontal cortex: DLPFC) has been explored by means of different approaches and particularly through non-invasive brain stimulation techniques (transcranial magnetic and electric stimulation: TMS and tES). Here we summarize studies on tES application in FMS. The great majority of reports, based on direct currents (transcranial direct currents stimulation: tDCS) and targeting M1, showed efficacy on pain measures and less on cognitive and affective symptoms, even if several aspects as maintenance of therapeutical effects and optimal stimulation parameters remain to be established. Differently, stimulation of DLPFC, explored in a few studies, was ineffective on pain and showed limited effects on cognitive and affective symptoms. Very recently new tES techniques as high-density tDCS (HD-tDCS), transcranial random noise stimulation (tRNS) and tDCS devices for home-based treatment have been explored in FMS with interesting even if very preliminary results opening interesting perspectives for more effective, well tolerated, cheap and easy therapeutic approaches.

Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Application of protocols without parameter standardization and appropriate controls has led manual therapy (MT) and other physiotherapy-based approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way in which this can be achieved is by studying gene expression and physiological changes that associate to particular, parameter-controlled, treatments in animal models, and translating this knowledge to properly designed, objective, quantitatively-monitored clinical trials (CTs). Here, we propose a molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports that historically attribute health benefits to MT-treatments. The review focuses on the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The systemic effects associated to mechanical-load responses are considered of particular relevance, as they suggest that defined, low-pain anatomic areas can be selected for MT treatment and yet yield overall benefits, an aspect that might result in it being essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, which is particularly detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to improve FM and CFS/ME.

Juvenile Fibromyalgia: Different from the Adult Chronic Pain Syndrome?

While a majority of research has focused on adult fibromyalgia (FM), recent evidence has provided insights into the presence and impact of FM in children and adolescents. Commonly referred as juvenile fibromyalgia (JFM), youths, particularly adolescent girls, present with persistent widespread pain and cardinal symptoms observed in adult FM. A majority of youth with JFM continue to experience symptoms into adulthood, which highlights the importance of early recognition and intervention. Some differences are observed between adult and juvenile-onset FM syndrome with regard to comorbidities (e.g., joint hypermobility is common in JFM). Psychological comorbidities are common but less severe in JFM. Compared to adult FM, approved pharmacological treatments for JFM are lacking, but non-pharmacologic approaches (e.g., cognitive-behavioral therapy and exercise) show promise. A number of conceptual issues still remain including (1) directly comparing similarities and differences in symptoms and (2) identifying shared and unique mechanisms underlying FM in adults and youths.

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia.

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM.