Advanced Research on Fibromyalgia (2nd Edition)

Background/Objectives: Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and mental health issues. It affects approximately 1.78% of the general population; an estimated 4:1 ratio between women and men is observed. It significantly impacts quality of life and carries both clinical and social stigma. This study aims to evaluate the relationship between drug use and mental health in female patients with fibromyalgia. Methods: This study is prospective, observational, and cross-sectional. A questionnaire was administered to 544 subjects, achieving a representative sample size from a population of 800,000 subjects by using an algorithm for proportion estimation with a known sampling frame. The selection was non-random, making the sampling non-probabilistic. Logistic regression models were applied to assess the effect of drug use on perception of mental health; presence of symptoms such as comprehension and memory problems, insomnia, depression, and anxiety; and severity of cognitive symptoms and non-restorative sleep. To quantify the impact, odds ratios and confidence intervals have been observed. Results: The findings indicate the non-recommended use of medications and reveal the ineffectiveness and adverse effects of drug interactions on mental health. The use of benzodiazepines and sedative-hypnotics is significantly associated with a negative perception of mental health. Benzodiazepines do not improve symptoms or significantly reduce their severity. SSRI antidepressants do not enhance mental health perception; however, when used exclusively, they are effective in reducing the severity, but not the prevalence, of cognitive symptoms. Conclusions: The results highlight the complexity of pharmacological management in FM and raise concerns about the inappropriate use of ineffective or counterproductive drug interactions affecting patients’ mental health. They underscore the need for multidisciplinary and personalized strategies that include close and careful monitoring, as well as the simultaneous use of non-pharmacological treatments that have demonstrated evidence in improving quality of life without negatively affecting mental health, such as patient education, psychological therapy, physiotherapy, and mindfulness. Full article

Background/Objectives: Fibromyalgia (FM) is a syndrome characterized by widespread chronic pain as the primary symptom. Neurophysiological pain mechanisms, such as the function of the descending inhibitory system, are impaired in this condition. The main objective of this study was to compare the results of two paradigms to evaluate CPM in women with FM. The secondary objective was to correlate the results of each CPM paradigm with the clinical status of patients with FM. Methods: One hundred and three FM women were divided into two groups: fifty patients diagnosed with FM were assigned to the conditioned pain modulation (CPM) group using a cold pressor stimulus, and fifty-three patients were assigned to the CPM group using the ischemic pressure stimulus. The main outcome measures were pain intensity, disability, mechanical hyperalgesia, and CPM. Results: The primary analysis revealed significant differences between the results obtained from the different CPM protocols. Poorer outcomes in the cold pressor test correlated with higher pain intensity and a greater disability index. Conclusions: Pain modulation abnormalities in FM patients were evident when using either the cold pressor or ischemic pressure stimuli to establish the CPM paradigm. The cold pressor conditioning stimulus elicited a stronger response than the ischemic pressure stimulus in FM patients. Full article

New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK pain post-COVID-19 and assessed the nature of the pain and associated symptoms using the C19-YRS (Yorkshire Rehabilitation Scale). The FMS assessment was conducted as part of a standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria: (1) Widespread Pain Index (WPI) ≥ 7 and symptoms severity (SS) score ≥ 5, or WPI between 3 and 6 and SS score ≥ 9, (2) symptoms consistent for at least 3 months, and (3) no alternative diagnosis. Of the eighteen patients (average age 49.6 (SD 11.8) years; BMI 31.7 (SD 8.6)), twelve were female. The average symptom duration was 27.9 (SD 6.97) months post-infection. Thirteen patients (72.2%) met the FMS criteria, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant quality of life impacts. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions. Full article

Background: Evidence suggests that aerobic training with blood flow restriction is beneficial for treating fibromyalgia. This study evaluated the feasibility, safety, and effects of an aerobic training program with blood flow restriction for women with fibromyalgia. Methods: Thirty-seven women with fibromyalgia were included, and thirteen with an average age of 59 ± 3, a BMI of 26 ± 3, and who were polymedicated started the intervention period. The intervention group performed aerobic exercise with blood flow restriction using occlusive bands placed in the upper part of the rectus femoris, with a total duration of 14 min of restriction divided into two periods of 7 min with a rest period of 3 min and a total session duration of 17 min. Pressure intensity was measured using the visual pain scale (VAS), scoring 7 out of 10 (n = 7). The non-intervention group performed aerobic exercise without restriction of blood flow for the same periods, rest periods, and total duration of the session (n = 6). The intervention included 2 weekly sessions with 72 h between aerobic walking for 9 weeks. Walking was measured individually using the rating of perceived exertion scale (RPE) with an intensity between 6 and 7 out of 10. Visual and verbal support for the VAS and RPE scale was always provided throughout the sessions supervised by the investigator. Functional capacity was assessed using tests (six-minute walk test, incremental shuttle walk test, knee extension and handgrip test by dynamometer, 30 s chair stand test, and timed up-and-go test). Symptomatology was assessed using questionnaires (Widespread Pain Index, Symptom Severity Score, Fibromyalgia Impact Questionnaire, and Multidimensional Fatigue Inventory), and blood samples were collected. Results: There were no adverse effects, and only one participant in the intervention group withdrew. Between-group and intragroup differences showed that the intervention group obtained improvements in the functional tests; CST p = 0.005; 6MWT p = 0.011; Handgrip p = 0.002; TUGT p = 0.002 with reduced impact of the disease according to the questionnaires; FIQ Stiffness p = 0.027 compared with the nonintervention group. Biochemical results remained within normal ranges in both groups. Conclusions: Blood flow-restricted aerobic training may be feasible, safe, and more effective than unrestricted aerobic training as a physical exercise prescription tool to improve cardiorespiratory fitness, strength, balance, and stiffness in women with fibromyalgia. Full article

(1) Background: The main characteristic of fibromyalgia (FM) is generalized musculoskeletal pain. This may be accompanied by muscle and joint stiffness, sleep and mood disorders, anxiety and depression, cognitive dysfunction, and chronic fatigue. It is endemic in developed countries, with a higher prevalence among women than men, and its etiology is still unknown. Diagnosis is made based on chronic generalized pain and through the presence of tender points. The objective of this study was to analyze the efficacy of diathermy on pain in patients with fibromyalgia. (2) Methods: A single, blind, randomized experimental study was developed with a sample of 31 participants. Measurements were taken and recorded at three different intervals using the following measurement tools: the pressure pain threshold (PPT) at the tender points (TP) of the right and left trochanteric prominence with an algometer, the pain measurement scale, the Fibromyalgia Impact Questionnaire, the sleep quality index (PSQI, Pittsburgh), the Multidimensional Fatigue Inventory (MFI-S), and the scale for anxiety and depression (Hospital Anxiety and Depression Scale). Sociodemographic data were collected through Google Forms (age, height, weight, Body Mass Index). The intervention took place twice weekly across four weeks of sessions. (3) Results: Statistically significant results were obtained in the right and left trochanter PPT, as well as for anxiety and fatigue in the experimental group. The results obtained show that this treatment has managed to improve the quality of sleep, the impact of disease, chronic fatigue, and anxiety in patients with FM. (4) Conclusions: Diathermy is a tool that can help reduce pain. It can also improve the baseline levels of chronic fatigue, anxiety, the impact of the disease, and sleep quality in patients with fibromyalgia. Full article

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10–20% of individuals following COVID-19 infection. FM and LC share similarities with regard to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface-enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCAs) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n = 48 FM and n = 46 LC) and volumetric absorptive micro-sampling tips (VAMS, n = 39 FM and n = 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra were acquired using SERS with gold nanoparticles (AuNPs). Soft independent modelling of class analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity, achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNP SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC. Full article

Background: Fibromyalgia (FM) is a chronic pain disorder and is associated with disability, and high levels of pain and suffering. FM is known to co-occur with obesity and obstructive sleep apnea (OSA). Individuals with FM often experience symptoms of pain, depression and anxiety, sleep disturbances, and fatigue. These symptoms may be exacerbated by OSA and contribute to the symptoms’ severity in FM. Obesity is a common comorbidity in OSA patients, and as FM and OSA are related in some patients, obesity also may contribute to FM symptom severity. For healthcare providers to effectively manage FM patients, a better understanding of the co-occurrence between these FM comorbidities and psychological factors is needed. Methods: This study was approved by IRB and conducted using a retrospective EPIC chart review. To identify FM, the following ICD-9 codes were used: (729.1) and ICD-10 (M79.7) codes. To identify patients with OSA, the following ICD-9 codes were used: (327.23) and ICD-10 (G47.33). Body Mass Index (BMI), the total number of medical diagnoses, and psychiatric conditions were documented for each patient. The prevalence of psychiatric conditions including depression and anxiety was compared between patients with and without obesity (BMI > 30), and patients with fewer than 25 medical diagnoses and those with 25 or more diagnoses. A chart review was conducted to identify patients with fibromyalgia with prior serum cortisol testing within the last ten years. Cortisol levels were compared and patients were divided into six groups: 1. FM without identified psychiatric conditions; 2. FM with psychiatric diagnosis of adjustment disorders and insomnia; 3. FM with psychiatric diagnosis of depressive disorders; 4. FM with psychiatric diagnosis of bipolar disorders; 5. FM with psychiatric diagnosis of mixed anxiety and depression; 6. FM with psychiatric diagnosis of anxiety disorders. Available C-reactive protein (CRP) values were gathered. Results: The total FM and OSA population was N = 331. The mean age of the patient population was 63.49 years old, with 297 being female. The diagnoses mean was 31.79 ± 17.25 and the mean total psychiatric diagnoses was 2.80 ± 1.66. The mean BMI was 36.69 ± 8.86, with obesity present in 77.95% of the patients. A total of 66.99% of patients had comorbid anxiety and depression with 25 or more medical problems vs. 33.01% of patients who had fewer than 25 medical problems (odds ratio = 1.50). Patients with a BMI < 30 (N = 71) had rates of anxiety and depression at 64.79% and a mean total of 2.79 ± 1.66 psychiatric diagnoses, whereas patients with a BMI > 30 (N = 258) had rates of anxiety and depression at 61.63% (odds ratio = 1.28) and a mean total of 2.80 ± 1.66 psychiatric diagnoses. The most common other psychiatric conditions among FM/OSA patients included hypersomnia and substance use disorders. Cortisol data: Available cortisol results: FM n = 64, female: 59, male: 5, mean age: 63, average BMI: 38.8. The averages for serum cortisol alone for groups 1–6, respectively, are 9.06, 5.49, 13.00, 14.17, 12.25, and 16.03 μg/dL. These results indicate a relatively upward cortisol serum value by the addition of several psychiatric conditions, with the most notable being anxiety for patients with FM. CRP values were available for 53 patients with an average CRP of 4.14. Discussion: Higher rates of anxiety and depression were present in FM patients with 25 or more diagnoses. The odds ratios indicate that a patient with 25 or more medical problems was 1.5 times more likely to have anxiety and depression than those with fewer diagnoses. Additionally, those with a BMI > 30 were 1.3 times more likely to have anxiety and depression than those with a normal BMI. Conclusion: addressing psychological factors in FM and OSA is important as high healthcare utilization is common in patients with FM and OSA. Full article

Gait impairments have been found in women with fibromyalgia, reducing the physical activity possibilities in this population and leading to a negative correlation with fibromyalgia impact. The aim of this study was to analyze the individual and independent associations of moderate-to-vigorous physical activity (MVPA), sedentary time, fat percentage, and physical fitness with gait parameters in women with fibromyalgia. A total of 84 women with fibromyalgia were included. MVPA and sedentary time were assessed with accelerometry, fat percentage with bioimpedance analysis, and physical fitness with field-based fitness tests. Gait was assessed during a “6 min walk test” and categorized in velocity, cadence, step length, step cycle duration, unipedal stance phase, and bipedal stance phase. Individual relationships were analyzed by partial correlations and independent relationships by linear regressions, adjusting by age and height. MVPA, sedentary time, fat percentage, and physical fitness were correlated with most gait parameters (rpartial between |0.842| and |0.219|; p ≤ 0.05). Physical fitness was independently associated with all gait parameters (β between |0.346| and |0.761|; p ≤ 0.002). In addition, MVPA was independently associated with velocity and step length (β = 0.241 and 0.292; both p = 0.004), and fat percentage was associated with bipedal stance phase (β = 0.242; p = 0.049). Good levels of MVPA, physical fitness, and adequate weight balance are associated with improved gait parameters in women with fibromyalgia. Full article

Fibromyalgia (FM) is a complex, chronic, widespread pain syndrome that can cause significant health and economic burden. Emerging evidence has shown that neuroinflammation is an underlying pathological mechanism in FM. Toll-like receptors (TLRs) are key mediators of the immune system. TLR4 is expressed primarily in microglia and regulates downstream signaling pathways, such as MyD88/NF-κB and TRIF/IRF3. It remains unknown whether electroacupuncture (EA) has therapeutic benefit in attenuating FM pain and what role the TLR4 pathway may play in this effect. We compared EA with sham EA to eliminate the placebo effect due to acupuncture. We demonstrated that intermittent cold stress significantly induced an increase in mechanical and thermal FM pain in mice (mechanical: 2.48 ± 0.53 g; thermal: 5.64 ± 0.32 s). EA but not sham EA has an analgesic effect on FM mice. TLR4 and inflammatory mediator-related molecules were increased in the thalamus, medial prefrontal cortex, somatosensory cortex (SSC), and amygdala of FM mice, indicating neuroinflammation and microglial activation. These molecules were reduced by EA but not sham EA. Furthermore, a new chemogenetics method was used to precisely inhibit SSC activity that displayed an anti-nociceptive effect through the TLR4 pathway. Our results imply that the analgesic effect of EA is associated with TLR4 downregulation. We provide novel evidence that EA modulates the TLR4 signaling pathway, revealing potential therapeutic targets for FM pain. Full article

Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C-tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed. Full article

Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain, which may or may not be associated with muscle or joint stiffness, accompanied by other symptoms such as fatigue, sleep disturbances, anxiety, and depression. It is a highly prevalent condition globally, being considered the third most common musculoskeletal disorder, following lower back pain and osteoarthritis. It is more prevalent in women than in men, and although it can occur at any age, it is more common between the ages of thirty and thirty-five. Although the pathophysiology and etiopathogenesis remain largely unknown, three underlying processes in fibromyalgia have been investigated. These include central sensitization, associated with an increase in the release of both excitatory and inhibitory neurotransmitters; peripheral sensitization, involving alterations in peripheral nociceptor signaling; and inflammatory and immune mechanisms that develop concurrently with the aforementioned processes. Furthermore, it has been determined that genetic, endocrine, psychological, and sleep disorders may influence the development of this pathology. The accurate diagnosis of fibromyalgia remains challenging as it lacks specific diagnostic biomarkers, which are still under investigation. Nonetheless, diagnostic approaches to the condition have evolved based on the use of scales and questionnaires for pain identification. The complexity associated with this pathology makes it difficult to establish a single effective treatment. Therefore, treatment is multidisciplinary, involving both pharmacological and non-pharmacological interventions aimed at alleviating symptoms. The non-pharmacological treatments outlined in this review are primarily related to physiotherapy interventions. The effectiveness of physical exercise, both on land and in water, as well as the application of electrotherapy combined with transcranial therapy and manual therapy has been highlighted. All of these interventions aim to improve the quality of life of patients highly affected by fibromyalgia. Full article

Fibromyalgia is a chronic, widespread pain disorder that is strongly represented across the affective and cognitive dimensions of pain, given that the underlying pathophysiology of the disorder is yet to be identified. These affective and cognitive deficits are crucial to understanding and treating the fibromyalgia pain experience as a whole but replicating this multidimensionality on a preclinical level is challenging. To understand the underlying mechanisms, animal models are used. In this scoping review, we evaluate the current primary animal models of fibromyalgia regarding their translational relevance within the affective and cognitive pain realms, as well as summarize treatments that have been identified preclinically for attenuating these deficits. Full article

Around 20–30% of Fibromyalgia patients modify their dietary habits after diagnosis, including avoiding certain food groups such as cereals. In this systematic review, we used the PRISMA guidelines to select the main studies that have evaluated the effectiveness of restrictive diets, including elimination and vegetarian diets, in patients with Fibromyalgia. Data on vegetarian/vegan diets are more consistent than data on elimination diets due to higher quality and better results of the published studies. Although the results are favorable in most of the studies, their heterogenicity and the scarce and low quality of the evidence (small number of patients included, often non-randomized and uncontrolled studies and multiple confounding factors and biases) does not allow for a positive recommendation about these restrictive diets in Fibromyalgia patients. Several factors other than food restriction could influence the symptomatic and functional improvements observed after restrictive diets, such as the placebo effect, weight loss that often occurs, coexistence with gastrointestinal diseases and positive effects of unrestricted foods. We must advance more and improve in our knowledge of the effectiveness of restrictive diets and variables related to them before recommending them systematically to all patients with Fibromyalgia. Randomized, placebo-controlled trials with large sample sizes, longer follow-up periods and standardized outcome measures that explore predictors of dietary response are needed to better understand the relationship between Fibromyalgia and nutrition. Full article