Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1.

Fibromyalgia (FM), classified by ICD-11 with code MG30.0, is a chronic debilitating disease characterized by widespread pain, fatigue, cognitive impairment, sleep, and intestinal alterations, among others. FM affects a large proportion of the worldwide population, with increased prevalence among women. The lack of understanding of its etiology and pathophysiology hampers the development of effective treatments. Our group had developed a manual therapy (MT) pressure-controlled custom manual protocol on FM showing hyperalgesia/allodynia, fatigue, and patient's quality of life benefits in a cohort of 38 FM cases (NCT04174300). With the aim of understanding the therapeutic molecular mechanisms triggered by MT, this study interrogated Peripheral Blood Mononuclear Cell (PBMC) transcriptomes from FM participants in this clinical trial using whole RNA sequencing (RNAseq) and reverse transcription followed by quantitative Polymerase Chain Reaction (RT-qPCR) technologies. The results show that the salt-induced kinase SIK1 gene was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, this study compared the findings in a non-FM control cohort subjected to the same MT protocol, evidencing that those changes in SIK1 expression with MT only occurred in individuals with FM. This positions SIK1 as a potential biomarker to monitor response to MT and as a therapeutic target of FM, which will be further explored by continuation studies.

Telehealth-delivered cognitive behavioral therapy - a potential solution to improve sleep quality and normalize the salience network in fibromyalgia: a pilot randomized trial.

Our study investigated the associations between the clinical benefits of telehealth-delivered cognitive behavioral therapy for insomnia (tele-CBT-I) and the salience network in fibromyalgia (FM). Thirty-five FM patients with comorbid insomnia were recruited and assigned into two groups: the tele-CBT-I group (n = 17) or the treatment-as-usual (TAU) group (n = 18). At baseline and post-treatment, clinical status was assessed using standardized scales, including the Insomnia Severity Index (ISI), Brief Pain Inventory, Numeric Pain Rating scale, Beck Depression Intervention version II, Beck Anxiety Intervention, Situational Fatigue Scale, and Fibromyalgia Impact Questionnaires. Resting-state functional magnetic resonance imaging was collected. We compared within- and between-group differences in clinical changes and functional connectivity (FC) of the salience network. A factor analysis of significant FCs was performed. Correlation analyses between clinical symptoms and salience FCs were conducted. The tele-CBT-I group showed sleep quality improvements after treatment that were greater than those in the TAU group (p-value = 0.038). After treatment, tele-CBT-I decreased FCs of cortical regions and increased FCs of subcortical regions compared to the TAU group. Additionally, factor analysis grouped the significant FCs into cortical factors and subcortical factors. The cortical factor value, representing the involvement of specific cortical regions of the salience network by the factor analysis, was significantly associated with ISI scores in the tele-CBT-I group (p-value = 0.0002). In conclusion, tele-CBT-I might be an adjuvant approach to improve sleep quality and normalize cortical and subcortical functions of the salience network in FM patients with comorbid insomnia.

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases.

Recognizing and Treating Major Depression in Fibromyalgia: A Narrative Primer for the Non-Psychiatrist.

Fibromyalgia (FM) affects 2% to 8% of the general population. FM patients often experience self-stigma and feel rejected by healthcare providers and families, resulting in isolation and distressing symptoms of pain, fatigue, and poor cognitive functioning, increasing the risk of depressive symptoms. Major Depressive Disorder (MDD) is the most common comorbidity in FM patients (Any depression: 43%; MDD: 32%). Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia. Given that even minor symptoms of depression worsen the outcomes of FM patients, clinicians are challenged to identify and manage depression in these patients. However, due to overlapping symptoms, limited screening, and contamination bias, MDD often goes undiagnosed and presents a critical challenge. Unrecognized and untreated MDD in FM patients can exacerbate fatigue, sleep disturbances, and pain, reduce physical functioning, and increase the risk of developing comorbid conditions, such as substance abuse and cardiovascular disease. These comorbidities are associated with a lower treatment response rate, a higher dropout rate, and a greater risk of relapse. Clinicians may effectively identify and treat MDD in FM patients with appropriate pharmacologic agents combined with aerobic exercise and cognitive-behavioral therapies for core FM symptoms, thus significantly reducing symptom severity for both MDD and FM. Such a comprehensive approach will result in a much-improved quality of life. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. In this primer for clinicians caring for FM patients, we describe clinically relevant pharmacologic and non-pharmacologic management approaches for treating MDD in FM patients.

Intravenous Magnesium for the Management of Chronic Pain:An Updated Review of the Literature.

Background: Available therapeutic options are currently limited by their modest efficacy. As a result, novel pharmacotherapeutic treatments with different mechanisms have recently attracted empirical attention. Magnesium, a divalent cation, is postulated to provide analgesic and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) receptor. Objective: Considering the evidence surrounding magnesium's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of magnesium's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of magnesium in the treatment of chronic pain from database inception to May 2022. Results: A total of 33 studies were included in the narrative review, out of which 26 were randomized controlled trials. Findings on available studies suggest that intravenous infusion of magnesium is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous magnesium is currently equivocal for a variety of chronic pain syndrome. Findings indicate that evidence for efficacy is poor or equivocal for: CRPS, neuropathic pain, chronic low back pain, and migraine prophylaxis. However, there is good evidence supporting the efficacy of intravenous magnesium for treating renal colic pain and pelvic pain related to endometriosis. Conclusion: Magnesium may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of magnesium in attenuating pain signaling pathways.

The determinants associated with the prescription of a first biologic therapy in patients with axial spondyloarthritis and concomitant fibromyalgia are mostly objective and in line with the recommendations. Results of a cross-sectional survey-based study using a mixed (qualitative and quantitative) approach to help rheumatologists in their daily practice.

OBJECTIVES: There is no consensus on the therapeutic strategy of rheumatologists for patients with spondyloarthritis (SpA) and concomitant fibromyalgia (FM).The main aim of this study was to identify, in a population of rheumatologists practicing in Normandy, France, the determinants associated with their decision to prescribe a first biologic DMARD (bDMARD) in patients with Spa/FM. Specific objectives were to evaluate professional prescribing practices to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists, and to validate the relevance of these criteria. METHOD: This is a cross-sectional survey-based study using a mixed (qualitative and quantitative) method. The quantitative approach was web-based and conducted among rheumatologists in Normandy. RESULTS: The qualitative study allowed us to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists. In the quantitative study, 54/113 rheumatologists filled the questionnaire. Four criteria were considered by all respondents to contribute to their decision to prescribe a first bDMARD: arthritis on physical examination, extra-articular manifestations, systemic inflammation and structural damage on imaging. CONCLUSIONS: The determinants associated with the decision of rheumatologists to prescribe a first bDMARD in patients with SpA/FM were mostly objective, in line with the recommendations in the literature. Most criteria were more related to an approach aimed at ensuring the diagnosis of SpA than evaluating its activity or severity.

Pain neuroscience education and motor imagery-based exercise protocol for patients with fibromyalgia: A randomized controlled trial.

BACKGROUND: This study is a randomized controlled, biopsychosocial study investigating the effectiveness of pain neuroscience education (PNE) and motor imagery-based exercise protocol (MIEP) on fibromyalgia pain. METHODS: Our study has four groups (MIEP n = 12, PNE n = 12, MIEP + PNE n = 14, Control n = 12) and all participants (n = 50) consist of patients diagnosed with fibromyalgia with chronic back pain. The primary outcome measure was pain intensity, and secondary outcome measures were beliefs, kinesiophobia, anxiety-depression, cognitive-mood, self-esteem, and body awareness. RESULTS: A statistically significant decrease in pain intensity was observed in all experimental groups, without any group being superior (Visual Analog Scale [VAS]: MIEP + PNE p = .003, 95% confidence interval [CI], -4.7078 to -0.9922; MIEP p = .003, 95% CI, -5.4806 to -1.0194; PNE p = .002, 95% CI, -3.6139 to -1.5461). There was a significant improvement in organic beliefs in both groups where PNE was applied (MIEP + PNE: p = .017, 95% CI, -7.8211 to -0.3189; PNE: p = .003, 95% CI, -9.7999 to -0.0401). A significant superiority in organic pain beliefs was detected in the MIEP + PNE group compared to the control group (p = .008, 95% CI, 1.7241-9.4959). CONCLUSIONS: According to this study, in which MIEP and PNE were combined, there was a decrease in pain intensity when both applications were applied together and when they were applied one by one. MIEP has improved her motor imagery ability, improved pain and increased body awareness. PNE has improved people's organic pain beliefs; removed people from fears, catastrophizing, and negative thoughts about pain; improved easier management of psychological processes and cognitive-emotion regulation ability.

Association between celiac disease and fibromyalgia and their severity: a cross-sectional study.

Background: Fibromyalgia (FMS) is a common musculoskeletal disorder with many causes. People with fibromyalgia often have the same symptoms as people with celiac disease (CD). Demonstration of the coordination and frequency of FMS and CD is important for effective treatment. Methods: This is a single center cross-sectional clinical study. The study included 60 patients who were diagnosed with CD by the Gastroenterology Clinic based on American College of Gastroenterology (ACG) criteria. Patients were also asked to complete the Widespread Pain Index (WPI), Symptom Severity Scale (SSS), and Fibromyalgia Impact Questionnaire (FIQ) to diagnose fibromyalgia and assess its severity. The results were used to analyze the frequency of concomitance and relationship between the two diseases. Results: The relationship between the clinical types of CD and the presence of fibromyalgia was insignificant. Analysis of the relationship between the pathologic typing of biopsy and fibromyalgia frequency was insignificant. Those with antibodies more frequently met criteria for fibromyalgia (P = 0.04, P = 0.04, respectively). Conclusions: Presence of clinical extraintestinal manifestations in patients with CD should lead clinicians to consider FMS as a possible diagnosis. This points to the importance for clinicians in all subspecialties to be aware of the various symptoms and diseases associated with FMS.

Quality of Life Among Hospitalized Fibromyalgia Older Adults: a Case-Control Study.

Background: Only few studies addressed the topic of Fibromyalgia Syndrome (FMS) effects on geriatric population quality of life and drug usage. The objective of this study was to demonstrate the significant impact of FMS in terms of quality of life (QOL) in geriatric aged patients. Methods: 80 patients were studied, 40 with FMS according to FMS 2016 classification criteria, and 40 non-FMS controls. The patients were all above the age of 65 years. The FMS and control group completed Widespread Pain Index (WPI) and Symptom Severity Score (SSS). Three questionnaires, Fibromyalgia Impact Questionnaire (FIQ), Short Form (SF-36) Questionnaire, and Health Assessment Questionnaire Disability Index (HAQ-DI) were completed. These with additional medical records were used to classify symptoms and severity in both groups. Results: Fibromyalgia patients demonstrated significant higher disability scores, (FIQ of 79.5 vs. 33.9, p<.01, and HAQ-DI of 2.00 vs. 1.00, p<.01 for FMS vs. non-FMS, respectively), and lower social functioning in comparison to non-FMS controls (SF-36 of social functioning 0.31 vs. 0.92, p<.01 for FMS vs. non-FMS, respectively). The FMS group had a higher use of pain management medications (opioid use of 12 patients vs. 0, p<.01, use of non-steroidal anti-inflammatory drugs by 11 FMS patients vs. 4 non-FMS controls, p<.01). Conclusions: Patients with FMS older than 65 years of age demonstrate poorer outcomes and worse symptoms in comparison to matched-aged non-FMS control group. An association was found between FMS and the effect on the quality of life in this population.

Can electroencephalography (EEG) identify the different dimensions of pain in fibromyalgia? A pilot study.

BACKGROUND: Electroencephalography (EEG) is a promising tool for identifying the physiological biomarkers of fibromyalgia (FM). Evidence suggests differences in power band and density between individuals with FM and healthy controls. EEG changes appear to be associated with pain intensity; however, their relationship with the quality of pain has not been examined. We aimed to investigate whether abnormal EEG in the frontal and central points of the 10-20 EEG system in individuals with FM is associated with pain's sensory-discriminative and affective-motivational dimensions. The association between EEG and the two dimensions of emotional disorders (depression and anxiety) was also investigated. METHODS: In this cross-sectional pilot study, pain experience (pain rating index [PRI]) and two dimensions of emotional disorders (depression and anxiety) were assessed using the McGill Pain Questionnaire (PRI-sensory and PRI-affective) and Hospital Anxiety and Depression Scale (HADS), respectively. In quantitative EEG analysis, the relative spectral power of each frequency band (delta, theta, alpha, and beta) was identified in the frontal and central points during rest. RESULTS: A negative correlation was found between the relative spectral power for the delta bands in the frontal (r= -0.656; p = 0.028) and central points (r= -0.624; p = 0.040) and the PRI-affective scores. A positive correlation was found between the alpha bands in the frontal (r = 0.642; p = 0.033) and central points (r = 0.642; p = 0.033) and the PRI-affective scores. A negative correlation between the delta bands in the central points and the anxiety subscale of the HADS (r = -0.648; p = 0.031) was detected. CONCLUSION: The affective-motivational dimension of pain and mood disorders may be related to abnormal patterns of electrical activity in patients with FM. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov (NCT05962658).

Fibromyalgia in patients infected with HTLV-1 and HTLV-2.

Background: Reports on the association between HTLV-2 infection and the development of diseases in the human host are rare, which has led the scientific community to believe that HTLV-2 is not an important etiological agent of lymphoproliferative or neurodegenerative disorders, which is the case for HTLV-1. In the present study, we demonstrated cases of fibromyalgia in HTLV-1 carriers and, in an unprecedented finding, in two patients with confirmed HTLV-2 infection. Methods: A total of 957 individuals visited the Virology Laboratory at the Federal University of Pará for screening and confirmation tests for HTLV-1/2 infection. Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms associated with infection. Results: Sixty-nine individuals (7.2%) were identified as positive for HTLV infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 cases of HTLV-2 infection (1.2%) and one case classified as undetermined (0.1%). Sixteen (23.2%) of these patients presented with rheumatological signs and complained of diffuse pain throughout the body; 12 of whom were infected by HTLV-1 (75%) and 4 were infected by HTLV-2 (25%). After anamnesis and careful evaluation, four patients were diagnosed with fibromyalgia, two of whom were infected by HTLV-1 (16.7%; 2/12) and two by HTLV-2 (50%; 2/4). The clinical follow-up and laboratory analysis results are reported in detail in this paper. Conclusion: Considering the clinical cases presented herein as the first reports of patients with HTLV-2 infection with clinical symptoms of fibromyalgia, the importance of further studies on the pathogenicity of HTLV-2, similar to what have already been performed for HTLV-1, is highlighted. Our results also confirm previous evidence of an association between HTLV-1 infection and fibromyalgia.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study.

INTRODUCTION: Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes. METHODS: In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy. RESULTS: IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (p < 0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all p < 0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: p = 0.002 and p = 0.003; pressure: both p < 0.001) and WUR (both p < 0.001). FMS participants exhibited reduced corneal nerve fibre density (p = 0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all p < 0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23). CONCLUSION: Participants with SFP, in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.

In people with painful idiopathic neuropathy (pain related to nerve damage where the cause of nerve damage is unknown), fibromyalgia syndrome (a long-term condition causing widespread pain), and healthy volunteers, the small nerve fibres of the peripheral nervous system, which may be involved in generating pain were assessed. These nerve fibres can be measured at the front of the eye (cornea) which can provide details on whether they are damaged in the body. The response to temperature, light touch, pressure and pinprick stimuli can also be used to determine if there is a loss or gain of sensation, which may contribute to pain. The aim of this study was to identify the degree of damage to these nerve fibres and to determine whether this damage is associated with a loss (cannot feel or requires more intense stimulus to feel) or gain (stimulus is felt earlier or is painful earlier at lower intensity) of sensory function. The pattern of loss or gain in sensory function is known as a sensory phenotype. It was found that people with painful idiopathic neuropathy had more severe nerve damage, loss of function to temperature and touch, and fewer small nerve fibres in the cornea compared to those with fibromyalgia syndrome and healthy volunteers. People with fibromyalgia syndrome were more sensitive to heat and pressure and had fewer corneal nerve fibres relative to healthy volunteers. The presence of corneal nerve fibre damage was associated with sensory phenotypes (types of sensation felt) in painful idiopathic neuropathy but not in fibromyalgia syndrome.

Adherence to ACSM exercise guidelines and its influence on Fibromyalgia treatment outcomes: a meta-analysis of randomized controlled trials.

Background: The Fibromyalgia Syndrome (FMS) is a multifaceted chronic pain disorder that exerts a substantial impact on the overall state of health and quality of life of patients. Purpose: Investigate the effects of exercise therapy and adherence to the American College of Sports Medicine (ACSM) guidelines on treatment outcomes in FMS patients. Methods: The literature search, which concluded in October 2023, encompassed studies investigating the impact of exercise interventions on patients diagnosed with FMS and providing adequate data for calculating standardized mean difference (SMD). The primary outcome measures encompassed the Fibromyalgia Impact Questionnaire (FIQ) and Health Assessment Questionnaire (HAQ), while secondary outcome measures comprised pain levels, sleep quality, fatigue, and mental health. Results: Among 4,008 records, 19 studies (patients = 857) were eligible for qualitative synthesis. The meta-analysis revealed that the SMD for overall state of health impact was -0.94 (95%CI -1.26, -0.63), and the pooled SMD for the subgroup with high adherence to ACSM guidelines was -1.17 (95%CI -1.65, -0.69). The SMD for the subgroup with low or uncertain adherence was -0.73 (95%CI -1.12, -0.34). The overall effects included a -1.21 (95%CI -1.62, -0.79) SMD for pain relief, with high adherence achieving a -1.32 (95%CI -2.00, -0.64) SMD and low adherence a -1.06 (95%CI -1.55, -0.57) SMD. Mental health improvements showed a -0.95 (95%CI -1.32, -0.57) overall SMD, with high and low adherence subgroups at -0.96 (95%CI -1.62, -0.30) and -0.94 (95%CI -1.29, -0.60), respectively. Sleep quality impact was -1.59 (95%CI -2.31, -0.87) overall, with high adherence at -1.71 (95%CI -2.58, -0.83) and low adherence at -1.11 (95%CI -1.88, -0.33). Fatigue impact had a -1.55 (95%CI -2.26, -0.85) overall SMD, with -1.77 (95%CI -3.18, -0.36) for high adherence and -1.35 (95%CI -2.03, -0.66) for low adherence. Conclusion: Exercise therapy can improve the overall state of health, pain, sleep, and fatigue of FMS patients, particularly when adhering to ACSM guidelines. However, adherence levels do not affect mental health gains, indicating a need for future research on psychological impact. Systematic Review Registration: https://inplasy.com/inplasy-2024-3-0106/, identifier INPLASY202430106.

Comparative efficacy of neuromodulation and structured exercise program on pain and muscle oxygenation in fibromyalgia patients: a randomized crossover study.

Introduction: This study investigates the comparative efficacy of neuromodulation therapy using the EXOPULSE Mollii Suit and a structured exercise program in pain modulation and muscle oxygenation in Fibromyalgia patients. Methods: A randomized, crossover, longitudinal, and experimental study design was employed, involving 10 female Fibromyalgia patients. Participants were subjected to two distinct treatment modalities: neuromodulation therapy with the EXOPULSE Mollii Suit and a strength-based High-Intensity Interval Training (HIIT) exercise program, each conducted over 16 sessions. Outcome measures included pain severity, assessed using the Numeric Rating Scale (NRS), and muscle oxygenation variables measured via Near-Infrared Spectroscopy (NIRS). Results: Both interventions demonstrated significant reductions in NRS scores and improvements in muscle oxygenation. However, the exercise program yielded more pronounced long term basal adaptations in muscle oxygenation compared to the neuromodulation therapy. Discussion: The findings underscore the potential of integrating non-pharmacological treatments, particularly structured exercise programs, in managing Fibromyalgia. While neuromodulation therapy presents a viable alternative, the exercise regimen's capacity to induce basal muscle oxygenation adaptations suggests its superiority in addressing the complex symptoms of Fibromyalgia. Furthermore, these therapeutic approaches may enhance patients' vocational values and employability opportunities by improving their functional capabilities and overall quality of life.

The Prevalence of Fibromyalgia in Rheumatoid Arthritis Patients Using the Fibromyalgia Assessment Screening Tool (FAST 4) Based on the Multidimensional Health Assessment Questionnaire (MDHAQ).

Introduction Fibromyalgia (FM) is characterized by widespread pain and fatigue, accompanied by symptoms such as decreased concentration, autonomic dysfunction, and abdominal pain. It can be either primary or secondary, notably to rheumatoid arthritis (RA). The Fibromyalgia Assessment Screening Tools (FAST 4), derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), is a composite tool allowing for the rapid screening of FM. Our primary objective is to determine the prevalence of FM among RA patients using the FAST 4 index. Secondary objectives include comparing the FAST 4 index with the FiRST score and describing the correlation between FM and RA activity and different factors associated with FM in RA patients. Methods This was an observational cross-sectional study including patients diagnosed with RA according to the ACR/EULAR criteria. The FAST questionnaire comprises four sections assessing pain and fatigue on a visual analog scale, painful joints reported by the patient, and a list of 60 symptoms. A FAST 4 score of ≥ 3/4 indicates a positive screening for FM. Demographics and disease features were compared using descriptive statistics. Univariate and multivariate analyses using logistic regression models were performed to calculate odds ratios (ORs) with 95% CI. The sensitivity and specificity of the FAST 4 index were evaluated, and Fagan's nomograms were used to illustrate post-test probability. Statistically significant results were considered for p-values less than 0.05. Results The study enrolled 97 patients diagnosed with RA. The mean age of the patients was 56 ± 12.7 years, with a predominance of females (90.7%, N=88). The mean duration of RA was 13.5 ± 8.69 years. RA activity measured by DAS 28-ESR showed that 40.2% (N=39) had high disease activity, 38.1% (N=37) had moderate disease activity, 11.3% (N=11) had low disease activity, and 10.3% (N=10) were in remission. The prevalence of comorbid FM, according to the FAST 4 index, was 30.9% (N=30). Based on the Multidimensional Health Assessment Questionnaire (MDHAQ), depression was observed in 66.7% (N=20) patients with FM, while anxiety was reported in 60% (N=18). Moreover, 30.4% of patients screened positive for FM using the FiRST score. The FAST 4 index detected FM patients defined by FiRST with a sensitivity of 78.6% and a specificity of 87.1%. The positive predictive value (PPV) was 73.3%, and the negative predictive value (NPV) was 90%. Univariate analysis revealed that a positive FAST 4 index was associated with the number of painful and swollen joints (p<0.001 and 0.03, respectively). Additionally, patients with a positive FAST 4 index showed higher DAS 28 scores (p=0.002). No significant association was found with CRP levels (p=0.328), ESR (p=0.499), or the use of biological treatments (p=0.146) or corticosteroids (p=0.940). In multivariate analysis, only depression remained a risk factor, increasing the risk sixfold with an OR of 5.917, 95% CI (1.91-18.3), p=0.002. Conclusion Our study suggests a high prevalence of concomitant FM in our population, highlighting the importance of screening for FM, particularly using the FAST 4 index based solely on the MDHAQ questionnaire.

Identifying the genetic association between the cerebral cortex and fibromyalgia.

Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (ß = -0.0035 mm, PIVW = 0.0265), fusiform region (ß = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (ß = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (ß = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis.

From fibrositis to fibromyalgia to nociplastic pain: how rheumatology helped get us here and where do we go from here?

Rheumatologists and rheumatology have had a prominent role in the conceptualisation of nociplastic pain since the prototypical nociplastic pain condition is fibromyalgia. Fibromyalgia had been previously known as fibrositis, until it became clear that this condition could be differentiatied from autoimmune disorders because of a lack of systemic inflammation and tissue damage. Nociplastic pain is now thought to be a third descriptor/mechanism of pain, in addition to nociceptive pain (pain due to peripheral damage or inflammation) and neuropathic pain. Nociplastic pain can occur in isolation, or as a co-morbidity with other mechanisms of pain, as commonly occurs in individuals with autoimmune disorders. We now know that the cardinal symptoms of nociplastic pain are widespread pain (or pain in areas not without evidence of inflammation/damage), accompanied by fatigue, sleep and memory issues. There is objective evidence of amplification/augmentation of pain, as well as of non-painful stimuli such as the brightness of lights and unpleasantness of sound or odors. Nociplastic pain states can be triggered by a variety of stressors such as trauma, infections and chronic stressors. Together these features suggest that the central nervous system (CNS) is playing a major role in causing and maintaining nociplastic pain, but these CNS factors may in some be driven by ongoing peripheral nociceptive input. The most effective drug therapies for nociplastic pain are non-opioid centrally acting analgesics such as tricyclics, serotonin-norepinephrine reuptake inhibitors and gabapentinoids. However the mainstay of therapy of nociplastic pain is the use of a variety of non-pharmacological integrative therapies, especially those which improve activity/exercise, sleep and address psychological co-morbidities.

The effectiveness of stretching exercises in patients with fibromyalgia: A systematic review.

Fibromyalgia is one of the most prevalent chronic pain disorders. Fibromyalgia is characterised by generalised pain. In addition, patients with fibromyalgia often have co-morbidity. Since no cure is available, the treatment is based on symptom management, with physical exercise being the recommended first-line treatment. Different exercise modalities have been examined, including the practice of stretching exercises. The aim of the systematic review is to summarise the efficacy of stretching exercises on fibromyalgia symptoms and to study the content and the quality of the current evidence. The review followed the recommendations of the PRISMA statement. The search for articles was performed in April 2023. We searched on MEDLINE, PubMed, CINAHL, Web of Science, SCOPUS, AMED, PEDro, ClinicalTrials.gov and the Cochrane Collaboration Trials Register. The search was updated in March 2024. The protocol was registered in PROSPERO. Risk of Bias was assessed using the Cochrane Risk of Bias tool, and quality assessment was performed using the GRADE approach. In total, 2586 studies were found in the database searches, of which nine were included in the analysis. The primary outcome was pain. Secondary outcomes were self-reported quality of life, fatigue and physical and mental functioning. The available evidence shows that stretching exercises may improve pain, health-related quality of life and physical and mental functioning, but the level of evidence is low. The main limitation is due to issues with the heterogeneity of the interventions and small sample sizes. Trial registration: PROSPERO registration number CRD42023399614. Key Points • Stretching exercises show promise in the treatment of fibromyalgia. They may improve pain, health-related quality of life, physical functioning and mental health, but the level of evidence is low. • This study goes beyond previous research by presenting a more comprehensive and detailed analysis of the content and methodological quality of the current evidence. • Further research with clearly outlined protocols must be carried out to advance our understanding of the benefits of stretching exercises on fibromyalgia symptoms.

Characteristics of patients with difficult-to-treat rheumatoid arthritis: a descriptive retrospective cohort study.

BACKGROUND: In 2021, an EULAR task force published a definition of difficult-to-treat rheumatoid arthritis (D2T RA). Our current knowledge of D2T RA with the EULAR definition is based on European and Asian cohorts, and no North American cohort has yet to be published. The aim of this study was to compare D2T RA patients to non-D2T RA who are good responders to advanced therapy, and to describe their evolution in an university health center patient cohort. METHODS: This is a retrospective single centre study of the medical records of all adults with RA on at least one biologic or target synthetic DMARD (b/tsDMARD). D2T RA group was defined according to the EULAR definition of D2T RA. The non-D2T RA group was defined as a b/tsDMARD good responder who had low-disease activity or remission for at least one year on 1 or 2 b/tsDMARD mechanism of action. We compared the patients' comorbidities, and history of b/tsDMARD use. Descriptive statistics and proportions were calculated. Kaplan-Meier analysis with log-rank test was used to estimate and compare median survival. RESULTS: Among the 417 patients, 101 (24%) were D2T RA and 316 (76%) were non-D2T RA. D2T RA group was slightly younger (63 ± 9 years versus 65 ± 12 years, p = 0.045), more likely to have concomitant non-inflammatory pain (28% versus 8%, p < 0.0001) and to discontinue at least one b/tsDMARD due to intolerance (39% versus 10%, p < 0.0001). In the D2T RA group, JAK inhibitors were associated with longer drug continuation when used as the third b/tsDMARD. Fewer patients were using corticosteroid at their most recent follow-up in this Canadian cohort compared to others (16% versus from 29 to 74%). CONCLUSION: Concomitant non-inflammatory pain was more prevalent in D2T RA patients compared to b/tsDMARD good responder non-D2T RA patients. Steroid-sparing strategies is possible even in D2T RA patients. Future prospective research may compare JAK inhibitors with other mechanisms of action in D2T RA.