Research

Open AccessArticle

Subjective Sleep Quality Versus Objective Accelerometric Measures of Sleep and Systemic Concentrations of Sleep-Related Hormones as Objective Biomarkers in Fibromyalgia Patients

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María Dolores Hinchado

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Eduardo Otero

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Isabel Gálvez

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Leticia Martín-Cordero

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María del Carmen Navarro

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Eduardo Ortega

Biomedicines 2023, 11(7), 1980; https://doi.org/10.3390/biomedicines11071980 - 13 Jul 2023

Viewed by 531

Abstract

Poor quality of sleep leads to an increase in severity of the symptoms associated with fibromyalgia (FM) syndrome and vice versa. The aim of this study was to determine if the poor perceived sleep quality in FM patients could be corroborated by objective [...] Read more.

Poor quality of sleep leads to an increase in severity of the symptoms associated with fibromyalgia (FM) syndrome and vice versa. The aim of this study was to determine if the poor perceived sleep quality in FM patients could be corroborated by objective physiological determinations. Perceived sleep quality was evaluated (through the Pittsburgh Sleep Quality Index) in 68 FM patients compared to an age-matched reference group of 68 women without FM. Objective sleep quality (measured using accelerometry), and systemic concentrations of sleep-related hormones (catecholamines, oxytocin, serotonin, and melatonin) were evaluated in two representative groups from the reference control group (n = 11) and FM patients (n = 11). FM patients reported poorer subjective sleep quality compared to the reference group. However, no significant differences were found in accelerometry parameters, except for a delay in getting in and out of bed. In addition, FM patients showed no significant differences in oxytocin concentration and adrenaline/noradrenaline ratio, as well as a lower serotonin/melatonin ratio. Poor perception of sleep quality in FM patients does not correspond to objective determinations. A dysregulation of the stress response could be associated with the delay in their resting circadian rhythm and difficulty falling asleep. This would be the cause that justifies the perceived lack of rest and the fatigue they feel when waking up. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Prevalence and Contextual Factors of Juvenile Fibromyalgia in a Population-Based Italian Sample of Children and Adolescents

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Susanna Maddali Bongi

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Giovanni Vitali Rosati

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Guglielmo Bonaccorsi

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Chiara Lorini

Biomedicines 2023, 11(6), 1583; https://doi.org/10.3390/biomedicines11061583 - 30 May 2023

Viewed by 925

Abstract

Juvenile Fibromyalgia (JFM) is poorly known, leading to delay in the identification of the syndrome. On the other hand, early diagnosis in children is important to prevent the worsening of the disease. This study aims to estimate the prevalence of JFM in an [...] Read more.

Juvenile Fibromyalgia (JFM) is poorly known, leading to delay in the identification of the syndrome. On the other hand, early diagnosis in children is important to prevent the worsening of the disease. This study aims to estimate the prevalence of JFM in an Italian population-based convenience sample, using different criteria (2010 and 2016 ACR, Yunus and Masi), by involving family pediatricians. It also aims to assess the relationships between JFM and contextual factors of the children and their parents, as well as to raise awareness of JFM among pediatricians. Children’s data were collected using an ad hoc electronic questionnaire. Overall, 7275 questionnaires were collected (48.5% females; mean age: 8.2 ± 3.6 years). Thirty-eight children (0.5%) met the 2010 ACR criteria, and 4 (0.1%) met the 2016 ACR criteria. The likelihood of meeting the 2010 ACR criteria was significantly higher for children older than 8 years (OR: 2.42), those who had injuries during the leisure time that caused persistent pain (OR: 6.49), whose parents (at least one) had a diagnosis of fibromyalgia (OR: 2.54) or diffuse pain (OR: 9.09). In conclusion, 2010 ACR criteria are confirmed as the more appropriate for children and adolescents and the analysis of contextual factors suggests the need for family pediatricians to pay particular attention to the most important predictors of JFM. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Influence of Chronic Fatigue Syndrome Codiagnosis on the Relationship between Perceived and Objective Psychoneuro-Immunoendocrine Disorders in Women with Fibromyalgia

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Eduardo Otero

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Isabel Gálvez

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Eduardo Ortega

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María Dolores Hinchado

Biomedicines 2023, 11(5), 1488; https://doi.org/10.3390/biomedicines11051488 - 20 May 2023

Cited by 1 | Viewed by 2422

Abstract

Although the predominant symptom in fibromyalgia (FM) is muscle pain, and fatigue in chronic fatigue syndrome (CFS), differential diagnosis is very difficult. This research investigates the psychoneuroimmunoendocrine disorders of FM patients and ascertains whether a previous CFS diagnosis affected them. Through accelerometry objective [...] Read more.

Although the predominant symptom in fibromyalgia (FM) is muscle pain, and fatigue in chronic fatigue syndrome (CFS), differential diagnosis is very difficult. This research investigates the psychoneuroimmunoendocrine disorders of FM patients and ascertains whether a previous CFS diagnosis affected them. Through accelerometry objective parameters, physical activity/sedentarism levels in relation to fatigue are studied, as well as whether perceived levels of stress, anxiety, and pain correspond to objective biomarkers, all of these with respect to a reference group (RG) of women without FM. FM patients have a worse psychological state and perceived quality of life than those with RG. These perceived outcomes are consistent with impaired objective levels of a sedentary lifestyle, higher systemic levels of cortisol and noradrenaline, and lower levels of serotonin. However, FM patients with a previous CFS diagnosis had lower systemic levels of IL-8, cortisol, oxytocin, and higher levels of adrenaline and serotonin than FM patients without diagnosed CFS. In conclusion, while perceived health parameters do not detect differences, when objective neuroimmunoendocrine parameters related to stress, inflammation, pain, and fatigue are used, people with CFS could be overdiagnosed with FM. This reinforces the need for objective biomarker assessment of these patients for better diagnostic discrimination between both syndromes. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Effectiveness of Vestibular Rehabilitation in Improving Health Status and Balance in Patients with Fibromyalgia Syndrome: A Single-Blind Randomized Controlled Trial

by

Ana Belén Peinado-Rubia

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María Catalina Osuna-Pérez

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Irene Cortés-Pérez

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Alicia Rojas-Navarrete

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María del Rocío Ibancos-Losada

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Rafael Lomas-Vega

Biomedicines 2023, 11(5), 1297; https://doi.org/10.3390/biomedicines11051297 - 27 Apr 2023

Viewed by 1164

Abstract

Background: Fibromyalgia Syndrome (FMS) is a highly prevalent health problem whose main symptom is widespread pain, although it presents as other manifestations, such as loss of balance, that seem to mainly affect visuo-vestibular information. Objective: to compare the effects of a Vestibular Rehabilitation [...] Read more.

Background: Fibromyalgia Syndrome (FMS) is a highly prevalent health problem whose main symptom is widespread pain, although it presents as other manifestations, such as loss of balance, that seem to mainly affect visuo-vestibular information. Objective: to compare the effects of a Vestibular Rehabilitation (VR) program versus those of a Conventional Physical Exercise (CPE) program on the health status of patients with FMS. Methods: A single-blind randomized controlled trial was performed. Patients with FMS were randomly assigned to VR or CPE programs. The protocols were performed in 40 min group sessions, twice weekly, for 16 sessions. Perceived health status, static and dynamic balance, verticality perception, confidence in balance, sensitization and kinesiophobia were measured at baseline, post-treatment and at the three-month follow-up and analyzed using an intention-to-treat approach. Results: Forty-eight subjects were randomly assigned, of whom thirty-five completed the planned VR (n = 19) or CPE (n = 16) program. At the three-month follow-up, there were differences in physical health status measured with the SF-12 (mean = −4.36, SE = 1.88, p = 0.027), balance during walking (mean = 1.90, SE = 0.57, p = 0.002), the perception of verticality in degrees (mean = 3.61, SE = 1.51, p = 0.024) and the anteroposterior position of the center of pressure (mean = −7.88, SE = 2.80, p = 0.009), as well as a decrease in the number of falls (mean = 0.98, SE = 0.44, p = 0.033), favoring the VR group. Conclusions: Vestibular Rehabilitation can be as beneficial as conventional exercise in improving the state of health in patients with Fibromyalgia Syndrome, providing additional improvements in physical health status, body balance, the perception of verticality and the number of falls. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Efficacy of Low-Dose Naltrexone and Predictors of Treatment Success or Discontinuation in Fibromyalgia and Other Chronic Pain Conditions: A Fourteen-Year, Enterprise-Wide Retrospective Analysis

by

C. Noelle Driver

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Ryan S. D’Souza

Biomedicines 2023, 11(4), 1087; https://doi.org/10.3390/biomedicines11041087 - 03 Apr 2023

Cited by 1 | Viewed by 6166

Abstract

Current pharmacologic treatments may provide limited analgesia in fibromyalgia and other chronic pain disorders. Low-dose naltrexone (LDN) has emerged as a potential analgesic option that has been minimally explored. This study aims to describe current real-world prescribing practices of LDN, to investigate if [...] Read more.

Current pharmacologic treatments may provide limited analgesia in fibromyalgia and other chronic pain disorders. Low-dose naltrexone (LDN) has emerged as a potential analgesic option that has been minimally explored. This study aims to describe current real-world prescribing practices of LDN, to investigate if patients have a perceived benefit of LDN in treating pain symptoms and to identify predictors associated with a perceived benefit or discontinuation of LDN. We evaluated all outpatient prescriptions for LDN prescribed for any pain indication in the Mayo Clinic Enterprise from 1 January 2009 to 10 September 2022. A total of 115 patients were included in the final analysis. The patients were 86% female, had a mean age of 48 ± 16 years, and 61% of prescriptions were for fibromyalgia-related pain. The final daily dose of oral LDN ranged from 0.8 to 9.0 mg, while the most common dose was 4.5 mg once daily. Of patients who reported follow-up data, 65% reported benefit in their pain symptoms while taking LDN. Adverse effects were reported in 11 (11%) patients and 36% discontinued taking LDN by the most recent follow-up. Concomitant analgesic medications were used by 60% of patients and were not associated with perceived benefit nor discontinuation of LDN, including concomitant opioids. LDN is a relatively safe pharmacologic option that may benefit patients with chronic pain conditions and warrants further investigation in a prospective, controlled, and well-powered randomized clinical trial. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

An Observational Study on Chronic Pain Biomarkers in Fibromyalgia and Osteoarthritis Patients: Which Role for Mu Opioid Receptor’s Expression on NK Cells?

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Costanza Maria Cristiani

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Cinzia Garofalo

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Lucia Carmela Passacatini

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Giuseppe Viglietto

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Antonio Sili Scavalli

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Biomedicines 2023, 11(3), 931; https://doi.org/10.3390/biomedicines11030931 - 17 Mar 2023

Cited by 2 | Viewed by 1050

Abstract

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. [...] Read more.

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells’ functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the “Mu opioid receptor reserve theory”. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Neck Pain in Fibromyalgia: Treatment with Exercise and Mesotherapy

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Luigi Giuseppe Tumminelli

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Alessandro Picelli

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Nicola Smania

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Giulia Letizia Mauro

Biomedicines 2023, 11(3), 892; https://doi.org/10.3390/biomedicines11030892 - 14 Mar 2023

Cited by 1 | Viewed by 1236

Abstract

Background and Objectives: Fibromyalgia is a very common musculoskeletal disease. The purpose of this study is to assess, on a population of fibromyalgic patients, the clinical efficacy of antalgic mesotherapy with diclofenac and thiocolchicoside in the treatment of cervical pain reduction for improvement [...] Read more.

Background and Objectives: Fibromyalgia is a very common musculoskeletal disease. The purpose of this study is to assess, on a population of fibromyalgic patients, the clinical efficacy of antalgic mesotherapy with diclofenac and thiocolchicoside in the treatment of cervical pain reduction for improvement of the functional capacity and quality of life of these patients. Materials and Methods: We conducted an observational study of 78 fibromyalgia patients recruited using our hospital database. Based on the different types of treatment received, the patients were divided into two groups: the treatment group (TG), who received antalgic mesotherapy with diclofenac, thiococolchicoside, and mepivacaina; and the placebo group (PG), who received mesotherapy with sodium chloride solution. Patients in both groups also received the same rehabilitation protocol of 20 sessions. The primary outcome evaluated was the extent of pain. The secondary outcomes were the functional capacity and quality of life. Results: Pain improved both in the treatment group (7.4 ± 1.2 vs. 5.1 ± 1.1; p < 0.05) and placebo group (7.5 ± 1.4 vs. 6.1 ± 1.6; p < 0.05). The treatment group, compared to the placebo group, also showed significant statistical improvements in functional capacity (NDI: 35.6 ± 5.23 vs. 19.3 ± 3.41; p < 0.05) and quality of life (SF-12: 18.3 ± 4.11 vs. 33.1 ± 2.41; p < 0.05). Conclusions: Mesotherapy treatment with diclofenac and thiocolchicoside is a safe and effective procedure in the management of neck pain in fibromyalgia patients in the short term in terms of pain reduction, functional recovery and quality of life. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Rapid Biomarker-Based Diagnosis of Fibromyalgia Syndrome and Related Rheumatologic Disorders by Portable FT-IR Spectroscopic Techniques

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Michelle M. Osuna-Diaz

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Katherine R. Sebastian

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Kevin V. Hackshaw

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Luis Rodriguez-Saona

Biomedicines 2023, 11(3), 712; https://doi.org/10.3390/biomedicines11030712 - 27 Feb 2023

Viewed by 1591

Abstract

Fibromyalgia syndrome (FM), one of the most common illnesses that cause chronic widespread pain, continues to present significant diagnostic challenges. The objective of this study was to develop a rapid vibrational biomarker-based method for diagnosing fibromyalgia syndrome and related rheumatologic disorders (systemic lupus [...] Read more.

Fibromyalgia syndrome (FM), one of the most common illnesses that cause chronic widespread pain, continues to present significant diagnostic challenges. The objective of this study was to develop a rapid vibrational biomarker-based method for diagnosing fibromyalgia syndrome and related rheumatologic disorders (systemic lupus erythematosus (SLE), osteoarthritis (OA) and rheumatoid arthritis (RA)) through portable FT-IR techniques. Bloodspot samples were collected from patients diagnosed with FM (n = 122) and related rheumatologic disorders (n = 70), including SLE (n = 17), RA (n = 43), and OA (n = 10), and stored in conventional protein saver bloodspot cards. The blood samples were prepared by four different methods (blood aliquots, protein-precipitated extraction, and non-washed and water-washed semi-permeable membrane filtration extractions), and spectral data were collected with a portable FT-IR spectrometer. Pattern recognition analysis, OPLS-DA, was able to identify the signature profile and classify the spectra into corresponding classes (Rcv > 0.93) with excellent sensitivity and specificity. Peptide backbones and aromatic amino acids were predominant for the differentiation and might serve as candidate biomarkers for syndromes such as FM. This research evaluated the feasibility of portable FT-IR combined with chemometrics as an accurate and high-throughput tool for distinct spectral signatures of biomarkers related to the human syndrome (FM), which could allow for real-time and in-clinic diagnostics of FM. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Autoantibody Correlation Signatures in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Association with Symptom Severity

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Varvara A. Ryabkova

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Natalia Y. Gavrilova

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Alina A. Poletaeva

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Alexander I. Pukhalenko

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Irina A. Koshkina

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Leonid P. Churilov

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Yehuda Shoenfeld

Biomedicines 2023, 11(2), 257; https://doi.org/10.3390/biomedicines11020257 - 18 Jan 2023

Cited by 2 | Viewed by 3288

Abstract

Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. [...] Read more.

Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. However, the natural AAb network is much more extensive, and has not been previously investigated in these disorders. The enzyme immunoassays ELI-Viscero-Test and ELI-Neuro-Test were used to determine changes in serum content of 33 natural AAb to neural, organ-specific and non-tissue-specific autoantigens (a) in 11 ME/CFS patients with comorbid FM; (b) in 11 ME/CFS patients without FM; (c) in 11 healthy controls. Individual AAb profiles and their correlation with some clinical symptoms were analyzed. Both patients with ME/CFS(−)FM and ME/CFS(+)FM were characterized by more frequent and pronounced deviations in the immunoreactivity to GABA-receptors than healthy controls. Although the level of other natural AAb did not differ between study groups, AAb correlation signatures were altered in patients compared to healthy controls. Both in patients and healthy controls the level of natural AAb to various neural and tissue-specific antigens correlated with the severity of fatigue, bodily pain, depression, anxiety, physical and mental health-related quality of life. Notably, widely different correlation patterns were observed between study groups. Findings from this pilot study provide some evidence that the homeostasis of autoimmune relationships, which are possibly a physiological part of our immune system, may be altered in FM and ME/CFS. The correlation of disease-induced perturbations in individual AAb profiles with some clinical symptoms may arise from the immune system’s ability to reflect qualitative and quantitative changes in antigenic composition of the body. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Sedentary Behavior and Pain after Physical Activity in Women with Fibromyalgia—The Influence of Pain-Avoidance Goals and Catastrophizing

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Biomedicines 2023, 11(1), 154; https://doi.org/10.3390/biomedicines11010154 - 07 Jan 2023

Cited by 1 | Viewed by 906

Abstract

Background: Fibromyalgia is characterized by chronic pain and fatigue that triggers a functional disability caused by the lack of activity. Pain catastrophizing may contribute to avoiding activity with the intention of managing pain levels. Based on the sedentary behavior with fibromyalgia, the present [...] Read more.

Background: Fibromyalgia is characterized by chronic pain and fatigue that triggers a functional disability caused by the lack of activity. Pain catastrophizing may contribute to avoiding activity with the intention of managing pain levels. Based on the sedentary behavior with fibromyalgia, the present study assessed the preference of pain-avoidance goals and pain catastrophizing as mediator and moderator variables, respectively, that influence pain perception after a 6-min-walking test. Methods: The sample was composed of 76 women with fibromyalgia (mean age = 55.05, SD = 7.70). Previous sedentary behavior, preference for pain-avoidance goals, and pain catastrophizing were evaluated before starting the walking-test. Subsequently, pain perception was evaluated. Results: A significant moderated-mediation model was found in which pain-avoidance goals mediated the relationship between sedentarism and pain after a walking-test, and pain catastrophizing moderated the relationship between the preference for pain-avoidance goals and pain perception. Specifically, high levels of pain catastrophizing contributed to increased pain perceptions after completing the test (B = 0.570, p = 0.03, CI 95% (0.09, 0.11)]. Conclusions: The results suggest that motivational interventions can improve the symptoms because their objectives are focused on managing conflict goals. These interventions should focus on catastrophic cognitions considering that pain catastrophizing is deemed to be one of the major inhibitors of physical activity in fibromyalgia. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Pathological Cycle between Pain, Insomnia, and Anxiety in Women with Fibromyalgia and its Association with Disease Impact

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Biomedicines 2023, 11(1), 148; https://doi.org/10.3390/biomedicines11010148 - 06 Jan 2023

Viewed by 1219

Abstract

Background: Pain, sleep disturbances, and mood disorders are considered common symptoms of fibromyalgia (FM). However, the interactions that are established between them and the implication that this has in the disease are not clear. The main objective of this study is to clarify [...] Read more.

Background: Pain, sleep disturbances, and mood disorders are considered common symptoms of fibromyalgia (FM). However, the interactions that are established between them and the implication that this has in the disease are not clear. The main objective of this study is to clarify the relationships established between insomnia, pain intensity and anxiety in women with FM. Additionally, the effect that the indicated pathological cycle between pain, insomnia and anxiety may have on the impact of the disease in these patients is explored. Methods: A total of 228 women diagnosed with FM participated in this study (mean age = 56.99 years, SD = 10.35). Measurements were conducted at two time points. Initially, the women completed self-report questionnaires about anxiety (The Hospital Anxiety and Depression Scale; HADS), sleep problems (The Insomnia Severity Index; ISI) and pain intensity (Brief Pain Inventory; BPI), and a week later, they answered questions about the impact of fibromyalgia (Fibromyalgia Impact Questionnaire- Revised; FIQ-R). For data analysis, models 4 and 6 of the Macro Process for SPSS were used. Results: Insomnia predicts higher levels of pain, which in turn predicts higher levels of anxiety, which in turn predicts a higher impact of fibromyalgia (B = 2.76, SE = 1.10, 95% CI = [0.79,5.11]). No significant results were found for the other interactions between the variables. Conclusions: Due to the clinical and scientific relevance of the insomnia–pain–anxiety pathological cycle and given the impact it has on FM, it is especially relevant to develop programs for patients with fibromyalgia based mainly on improving sleep quality. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

The Behavior of Muscle Oxygen Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia

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Biomedicines 2023, 11(1), 132; https://doi.org/10.3390/biomedicines11010132 - 04 Jan 2023

Viewed by 1554

Abstract

Previous studies have reported that people with fibromyalgia (FM) could suffer from mitochondrial dysfunction. However, the consumption of muscle oxygen during physical exercise has been poorly studied. Therefore, this study aimed to explore the response of muscle oxygen during a fatigue protocol in [...] Read more.

Previous studies have reported that people with fibromyalgia (FM) could suffer from mitochondrial dysfunction. However, the consumption of muscle oxygen during physical exercise has been poorly studied. Therefore, this study aimed to explore the response of muscle oxygen during a fatigue protocol in people with FM and healthy controls (HC). In addition, the peak torque and the total work were assessed. A total of 31 participants (eighteen were people with fibromyalgia and thirteen were healthy controls) were enrolled in this cross-sectional study. All the participants underwent a fatigue protocol consisting of 20 repetitions at 180°·s⁻¹ of quadriceps flexions and extensions using a Biodex System 3. The muscle oxygen saturation (SmO₂), total hemoglobin (THb), deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O₂Hb) values were measured using a portable near-infrared spectroscopy (NIRS) device. Significant differences between people with FM and healthy controls were found at baseline: SmO₂ (FM: 56.03 ± 21.36; HC: 77.41 ± 10.82; p = 0.036), O₂Hb (FM: 6.69 ± 2.59; HC: 9.37 ± 1.31; p = 0.030) and HHb (FM: 5.20 ± 2.51; HC: 2.73 ± 1.32; p = 0.039); during the fatigue protocol: SmO₂ (FM: 48.54 ± 19.96; HC: 58.87 ± 19.72; p = 0.038), O2Hb (FM: 5.70 ± 2.34; HC: 7.06 ± 2.09; p = 0.027) and HHb (FM: 5.69 ± 2.65; HC: 4.81 ± 2.39; p = 0.048); and in the recovery at three min and six min for SmO₂, O₂Hb and HHb (p < 0.005). Furthermore, healthy control values of SmO2, O2Hb and HHb have been significantly altered by the fatigue protocol (p < 0.005). In contrast, people with FM did not show any significant alteration in these values. Moreover, significant differences were found in the peak torque at extension (FM: 62.48 ± 24.45; HC: 88.31 ± 23.51; p = 0.033) and flexion (FM: 24.16 ± 11.58; HC: 42.05 ± 9.85; p = 0.010), and the total work performed at leg extension (FM: 1039.78 ± 434.51; HC: 1535.61 ± 474.22; p = 0.007) and flexion (FM: 423.79 ± 239.89; HC: 797.16 ± 194.37; p = 0.005). Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Do Psychological Factors Influence the Elastic Properties of Soft Tissue in Subjects with Fibromyalgia? A Cross-Sectional Observational Study

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Santiago Navarro-Ledesma

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María Aguilar-García

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Ana González-Muñoz

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Leo Pruimboom

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María Encarnación Aguilar-Ferrándiz

Biomedicines 2022, 10(12), 3077; https://doi.org/10.3390/biomedicines10123077 - 30 Nov 2022

Cited by 1 | Viewed by 938

Abstract

Nowadays, there is evidence related to the impact that psychological factors have on symptoms, specifically vegetative ones, and on the autonomic nervous system in patients with fibromyalgia (FM). However, there are no studies to correlate the level of association between psychological factors and [...] Read more.

Nowadays, there is evidence related to the impact that psychological factors have on symptoms, specifically vegetative ones, and on the autonomic nervous system in patients with fibromyalgia (FM). However, there are no studies to correlate the level of association between psychological factors and the elastic properties of tissue in the FM population. Elastic properties of soft tissue reflect age- and disease-related changes in the mechanical functions of soft tissue, and mechanical failure has a profound impact on morbidity and mortality. The study has a cross-sectional observational design with 42 participants recruited from a private clinic and rehabilitation service. The Pain Catastrophizing Scale, Tampa Kinesiophobia Scale and Self-Efficacy Scale were used to assess psychological factors. The elastic properties of the tissue in the characteristic painful points, which patients suffering from FM described, were assessed by strain elastography. A low and significant level of association was found between pain catastrophising scale (PCS) and the non-dominant lateral epicondyle (r = −0.318; p = 0.045). Kinesiophobia was found to be related to the dominant lateral epicondyle (r = 0.403; p = 0.010), the non-dominant knee (r = −0.34; p = 0.027) and the dominant forearm (r = 0.360; p = 0.010). Self-Efficacy showed a low level of association with the non-dominant supraspinatus (r = −0.338; p = 0.033) and the non-dominant medial epicondyle (r = −0.326; p = 0.040). Psychological factors and the elastic properties of tissue seem to be associated in patients suffering from FM. The most profound association between psychological factors and non-dominant parts of the body could be related to neglect and non-use of those parts of the body. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Effects of a Telerehabilitation Program in Women with Fibromyalgia at 6-Month Follow-Up: Secondary Analysis of a Randomized Clinical Trial

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Ignacio Hernando-Garijo

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Ricardo Medrano-de-la-Fuente

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Sandra Jiménez-del-Barrio

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María Teresa Mingo-Gómez

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Héctor Hernández-Lázaro

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Silvia Lahuerta-Martin

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Luis Ceballos-Laita

Biomedicines 2022, 10(12), 3024; https://doi.org/10.3390/biomedicines10123024 - 23 Nov 2022

Cited by 1 | Viewed by 801

Abstract

(1) Background: Telerehabilitation allows health professionals to monitor patients without face-to-face contact. The objective was to analyze the effects of a telerehabilitation program based on aerobic exercise in women with fibromyalgia at 6-month follow-up. (2) Methods: Participants were randomized into the telerehabilitation group [...] Read more.

(1) Background: Telerehabilitation allows health professionals to monitor patients without face-to-face contact. The objective was to analyze the effects of a telerehabilitation program based on aerobic exercise in women with fibromyalgia at 6-month follow-up. (2) Methods: Participants were randomized into the telerehabilitation group (n = 17) or the control group (n = 17). The telerehabilitation group performed 30 sessions of exercise for 15 weeks. The exercises were guided by video and adjusted by videocalls. Pain intensity, fibromyalgia impact, physical function, isometric strength and quality of life were measured at baseline and at 6 months after the end of the intervention. (3) Results: There were no between-group differences in pain intensity, fibromyalgia impact, physical function, isometric strength or quality of life at 6-month follow-up (p > 0.05). (4) Conclusion: A telerehabilitation exercise program based on aerobic exercises may not be an effective treatment for women with fibromyalgia at 6 months of follow-up due to the lack of between-group differences in any variable. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessArticle

Identification of Resting-State Network Functional Connectivity and Brain Structural Signatures in Fibromyalgia Using a Machine Learning Approach

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Nguyen Thanh Nhu

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David Yen-Ting Chen

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Jiunn-Horng Kang

Biomedicines 2022, 10(12), 3002; https://doi.org/10.3390/biomedicines10123002 - 22 Nov 2022

Cited by 2 | Viewed by 1305

Abstract

Abnormal resting-state functional connectivity (rs-FC) and brain structure have emerged as pathological hallmarks of fibromyalgia (FM). This study investigated and compared the accuracy of network rs-FC and brain structural features in identifying FM with a machine learning (ML) approach. Twenty-six FM patients and [...] Read more.

Abnormal resting-state functional connectivity (rs-FC) and brain structure have emerged as pathological hallmarks of fibromyalgia (FM). This study investigated and compared the accuracy of network rs-FC and brain structural features in identifying FM with a machine learning (ML) approach. Twenty-six FM patients and thirty healthy controls were recruited. Clinical presentation was measured by questionnaires. After MRI acquisitions, network rs-FC z-score and network-based gray matter volume matrices were exacted and preprocessed. The performance of feature selection and classification methods was measured. Correlation analyses between predictive features in final models and clinical data were performed. The combination of the recursive feature elimination (RFE) selection method and support vector machine (rs-FC data) or logistic regression (structural data), after permutation importance feature selection, showed high performance in distinguishing FM patients from pain-free controls, in which the rs-FC ML model outperformed the structural ML model (accuracy: 0.91 vs. 0.86, AUC: 0.93 vs. 0.88). The combined rs-FC and structural ML model showed the best performance (accuracy: 0.95, AUC: 0.95). Additionally, several rs-FC features in the final ML model correlated with FM’s clinical data. In conclusion, ML models based on rs-FC and brain structural MRI features could effectively differentiate FM patients from pain-free subjects. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Review

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Open AccessReview

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

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Biomedicines 2023, 11(4), 1119; https://doi.org/10.3390/biomedicines11041119 - 07 Apr 2023

Cited by 1 | Viewed by 2509

Abstract

This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the [...] Read more.

This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessFeature PaperReview

Fibromyalgia Pathophysiology

by

Michael Gyorfi

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Adam Rupp

and

Alaa Abd-Elsayed

Biomedicines 2022, 10(12), 3070; https://doi.org/10.3390/biomedicines10123070 - 29 Nov 2022

Cited by 2 | Viewed by 4850

Abstract

This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory [...] Read more.

This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory input. Genetic research has revealed familial aggregation of fibromyalgia and other related disorders like major depressive disorder. Dysfunctional pain processing may also be influenced by exposure to physical or psychological stressors, abnormal biologic reactions in the autonomic nervous system, and neuroendocrine responses. With more research the pathophysiology of fibromyalgia will be better understood, leading to more logical and focused treatment options for fibromyalgia patients. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessSystematic Review

Cannabis for the Treatment of Fibromyalgia: A Systematic Review

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Biomedicines 2023, 11(6), 1621; https://doi.org/10.3390/biomedicines11061621 - 02 Jun 2023

Viewed by 1938

Abstract

Fibromyalgia is a common disease syndrome characterized by chronic pain and fatigue in conjunction with cognitive dysfunction such as memory difficulties. Patients currently face a difficult prognosis with limited treatment options and a diminished quality of life. Given its widespread use and potential [...] Read more.

Fibromyalgia is a common disease syndrome characterized by chronic pain and fatigue in conjunction with cognitive dysfunction such as memory difficulties. Patients currently face a difficult prognosis with limited treatment options and a diminished quality of life. Given its widespread use and potential efficacy in treating other types of pain, cannabis may prove to be an effective treatment for fibromyalgia. This review aims to examine and discuss current clinical evidence regarding the use of cannabis for the treatment of fibromyalgia. An electronic search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus using Medical Subject Heading (MeSH) terms on all literature published up to October 2022. A follow-up manual search included a complete verification of relevant studies. The results of four randomized controlled trials (RCTs) and five observational studies (a total of 564 patients) that investigated the effects of cannabis on fibromyalgia symptoms were included in this review. Of the RCTs, only one demonstrated that cannabinoids did not have a different effect than placebo on pain responses. Overall, this analysis shows low-quality evidence supporting short-term pain reduction in people with fibromyalgia treated with cannabinoid therapeutics. Although current evidence is limited, medical cannabis appears to be a safe alternative for treating fibromyalgia. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessBrief Report

Prevalence of Genetic Diamine Oxidase (DAO) Deficiency in Female Patients with Fibromyalgia in Spain

by

Gülşah Okutan

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Eva Ruiz Casares

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Teresa Perucho Alcalde

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Guerthy Melissa Sánchez Niño

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Bruno F. Penadés

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Ana Terrén Lora

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Lorena Torrente Estríngana

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Sara López Oliva

and

Ismael San Mauro Martín

Biomedicines 2023, 11(3), 660; https://doi.org/10.3390/biomedicines11030660 - 22 Feb 2023

Cited by 2 | Viewed by 1872

Abstract

Diamine oxidase (DAO) is an enzyme that metabolizes intestinal histamine. Single nucleotide polymorphisms (SNPs) of the Amine Oxidase Copper Containing 1 (AOC1) gene can lead to low enzymatic activity or functionality in histamine metabolism. This study aimed to determine the prevalence [...] Read more.

Diamine oxidase (DAO) is an enzyme that metabolizes intestinal histamine. Single nucleotide polymorphisms (SNPs) of the Amine Oxidase Copper Containing 1 (AOC1) gene can lead to low enzymatic activity or functionality in histamine metabolism. This study aimed to determine the prevalence of DAO deficiency for four variants of the AOC1 gene, p.Thr16Met (rs10156191), p.Ser332Phe (rs1049742), p.His664Asp (rs1049793), and c.691G > T (rs2052129), in 98 Spanish women with fibromyalgia between the ages of 33 and 60 years, and compare the distribution of allelic and genotypic frequencies with those of European population samples in Hardy–Weinberg equilibrium extracted from the Allele Frequency Aggregator (ALFA) database. The patients’ DNA was extracted, and analyzed using SNPE Multiplex (Single Nucleotide Primer Extension). The prevalence of genetic DAO deficiency was 74.5% based on the four variants of the AOC1 gene. SNP deficits were found at frequencies of 53.1% for p.Thr16Met, 49% for c.691G > T, 48% for p.His664Asp, and 19.4% for p.Ser332Phe. The allele and genotypic frequencies of the women with fibromyalgia did not differ from the European population. Variants of the AOC1 gene that are associated with genetic DAO deficiency could serve as a disruptive biomarker in patients with fibromyalgia. This study was registered in ClinicalTrials.gov Identifier: NCT05389761. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessBrief Report

Myositis-Specific and Myositis-Associated Antibodies in Fibromyalgia Patients: A Prospective Study

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Biomedicines 2023, 11(3), 658; https://doi.org/10.3390/biomedicines11030658 - 22 Feb 2023

Viewed by 1148

Abstract

Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to [...] Read more.

Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to evaluate the prevalence of Myositis-Specific and Myositis-Associated Antibodies (MSA/MAA) in a cohort of FM patients. We enrolled 233 consecutive FM patients (defined according to the 2016 criteria) that did not report clinical signs of autoimmune disorders and followed them for at least one year. The patients were tested for MSA/MAA with immunoblotting. FM patients were seropositive for Antinuclear Antibodies (ANA) in 24% of cases, for MSA in 9%, and for MAA in 6%. A specific diagnosis of CTD was made in 12 patients (5.2%), namely, 5 cases of primary Sjögren’s Syndrome and 7 of Idiopathic Inflammatory Myopathy. Seropositive patients showed clinical features similar to those who were seronegative at baseline. A CTD diagnosis was associated with ANA positivity (p = 0.03, X² 4.9), the presence of a speckled pattern (p = 0.02, X² 5.3), positivity for MAA (p = 0.004, X² 8.1), and MSA (p = 0.003, X² 9.2). In conclusion, a non-negligible proportion of FM patients may be seropositive for MSA/MAA, and that seropositivity might suggest a diagnosis of CTD. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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Open AccessPerspective

Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment

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Biomedicines 2023, 11(2), 615; https://doi.org/10.3390/biomedicines11020615 - 18 Feb 2023

Viewed by 1458

Abstract

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and [...] Read more.

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic “weakening” in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia)

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