Environmental factors and fibromyalgia syndrome: a narrative review.

This in-depth review of fibromyalgia (FM), which is a complex condition characterised by chronic pain, fatigue, sleep disturbances, and a spectrum of diagnostically and therapeutically challenging symptoms, underlines the need for a comprehensive and integrated approach that also takes into account the psychological factors affecting patient responses. We focus on the substantial impact that environmental factors (climatic variations, air pollution, electromagnetic field exposure, physical and emotional traumas, dietary patterns, and infections) have on the manifestation and intensity of symptoms, and advocate personalised, holistic treatment of patients' psychological and environmental sensitivities by suggesting the benefits of tailored dietary and stress management. We also call for further research into the complex interplay of environmental, biological and psychological factors influencing FM in order to develop more effective individualised treatments that are capable of enhancing patient care and outcomes.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

[POST-COVID SYNDROME, SICK BUILDING SYNDROME, SILICONE BREAST SYNDROME, CHRONIC FATIGUE SYNDROME, FIBROMYALGIA; AUTOIMMUNITY TO THE AUTONOMIC NERVOUS SYSTEM].

INTRODUCTION: POST-COVID SYNDROME, SICK BUILDING SYNDROME, SILICONE BREAST SYNDROME, CHRONIC FATIGUE SYNDROME, FIBROMYALGIA; AUTOIMMUNITY TO THE AUTONOMIC NERVOUS SYSTEM.

Implication of intestinal microbiota in the etiopathogenesis of fibromyalgia: A systematic review.

Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

The preventive role of vitamin D in the prevention and management of Fibromyalgia syndrome.

Aim: Vitamin D deficiency is a prevalent condition among the general population, all around the world. Vitamin D deficiency is defined as serum levels of 25-hydroxy vitamin D lower than 20 ng/ml (50 nmol/ml). It is a known actor in the skeletal system through the regulation of calcium and phosphate metabolism and bone mineralization. Still, the role of vitamin D as an immunomodulator is yet to be acknowledged by healthcare practitioners as a cause, precipitating factor, and contributor to a variety of diseases. Vitamin D is shown to be an actor in multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and irritable bowel syndrome. Fibromyalgia syndrome (FMS) is a chronic disorder associated with a severe pain that can affect a patient's musculoskeletal system, daily routine, and mood. The clinical presentation encapsulates other disorders such as lethargy and sleep problems, brain fog and other cognitive issues, and physical and psychiatric symptoms. Methods: We have used PubMed and ResearchGate in the reviewing process of our paper. We tried to address as many topics as we judged to be adequate and relevant for the practicing clinicians. Results: Management of fibromyalgia syndrome is both nonpharmacologic and pharmacologic, which are provided in a stepwise fashion. Yet, the management of FMS remains a challenge, heeding a multidisciplinary approach. Among the dietary interventions, we chose vitamin D and its effects on FMS. Literature shows that supplementation improves pain caused by fibromyalgia syndrome, yet specific recommendations are still to be created. Conclusions: We call on all the relevant governmental bodies, public health experts and health policy makers, healthcare practitioners, and the civil society to use novel data related to fibromyalgia syndrome, and in a broader perspective, the integral role of vitamin D.

Does Fibromyalgia Affect the Outcomes of Spinal Cord Stimulation: An 11-Year, Multicenter, Retrospective Matched Cohort Study.

BACKGROUND: Fibromyalgia is a prevalent disorder manifesting with widespread musculoskeletal pain and central sensitization, as well as fatigue, sleep issues, psychologic distress, and poor quality of life. Patients with fibromyalgia also may be diagnosed with other painful conditions amenable to treatment with spinal cord stimulation (SCS), although it is unclear how these patients respond to SCS compared with patients without fibromyalgia. MATERIALS AND METHODS: We performed an 11-year, multicenter, retrospective matched cohort study comparing SCS-treated patients with fibromyalgia and those without fibromyalgia. The primary outcome was comparison in mean calculated percentage pain relief between cohorts at six months after SCS implantation. Secondary outcomes included comparison of patient satisfaction between six and 12 months after SCS implantation, and percentage of patients reporting opioid intake and neuropathic medication intake at six months and 12 months after SCS implantation. Adjusted regression analysis was performed to make comparisons while adjusting for age, sex, body mass index, Charlson comorbidity index, preoperative opioid intake, and preoperative neuropathic medication intake. RESULTS: Of 90 patients with fibromyalgia who underwent SCS trial, 18 patients (20%) failed their SCS trial and did not proceed toward implantation. Sixty-eight patients with fibromyalgia were matched to 141 patients in the control cohort based on age, sex, Charlson comorbidity index, and the American Society of Anesthesiologists physical status score. At six months after SCS implantation, there was no statistical difference in calculated percentage change in pain intensity between the fibromyalgia cohort (46.6 ± 29.0) and the control cohort (50.9 ± 32.8; ß, -18.4; 95% CI, -44.3 to 7.6; p = 0.157). At baseline, a greater percentage of patients in the fibromyalgia cohort reported preoperative opioid intake (51.5% vs 22.7%, p < 0.001) and preoperative neuropathic medication intake (67.6% vs 15.6%, p < 0.001). However, there was no difference between cohorts in the percentage of patients taking opioid or neuropathic medications at six months and 12 months after SCS implantation. Similarly, there was no difference between cohorts in the percentage of patients reporting satisfaction between six and 12 months. CONCLUSION: Patients with fibromyalgia who received a diagnosis approved for treatment with SCS may expect similar post-SCS-implantation pain relief, overall satisfaction, and analgesic use rate to those of patients without fibromyalgia.

Neuroimaging in Breast Implant Illness: An fMRI Pilot Study.

BACKGROUND: Some women with breast implants report systemic and cognitive symptoms known as breast implant illness (BII), which are very similar to those of fibromyalgia. Functional MRI (fMRI) has shown altered brain activity in fibromyalgia patients. OBJECTIVES: The aim of this pilot study was to investigate whether brain alterations could be observed in BII patients by fMRI. METHODS: Women aged 18 to 76 with silicone breast implants for cosmetic reasons were recruited through a Dutch online BII support organization (MKS) and through the Maastricht University Medical Center. Study participants comprised 12 women with BII and 12 women without symptoms. Participants completed questionnaires regarding demographic characteristics, medical history, psychosocial complaints (Four-Dimensional Symptom Questionnaire), cognitive failure (Mini-Mental State Examination), and pain intensity and pain-related disability (Chronic Pain Grade Scale). Subsequently, brain images of all participants were obtained by resting-state fMRI and diffusion tensor imaging in a 3-T MRI scanner (Siemens Medical System, Erlangen, Germany). RESULTS: Eleven BII patients and 12 healthy controls were included in the analysis. Baseline characteristics were similar in the 2 groups and the mean silicone exposure was 15 years. Patients scored significantly higher than controls on both pain intensity and disability. Patients scored worse on depression, somatization, distress, and anxiety compared with asymptomatic women. Mini-Mental State Examination scores were normal. However, the analyses of both functional connectivity and structural integrity showed no significant differences between the 2 groups. CONCLUSIONS: This pilot study showed no evidence of brain alterations in BII patients. However, patients scored significantly worse on psychosocial symptoms than controls. Psychological factors appear to play an important role in BII and should be further investigated.

Autoimmune autonomic nervous system imbalance and conditions: Chronic fatigue syndrome, fibromyalgia, silicone breast implants, COVID and post-COVID syndrome, sick building syndrome, post-orthostatic tachycardia syndrome, autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants.

Chronic fatigue syndrome (CFS), fibromyalgia, silicone breast implants syndrome (SBIs), COVID and post-COVID syndrome (PCS), sick building syndrome (SBS), post-orthostatic tachycardia syndrome (POTS), autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are frequently accompanied by clinical symptoms characteristic for dysautonomia: severe fatigue, dizziness, fogginess, memory loss, dry mouth and eyes, hearing dysfunction, tachycardia etc. The recent discovery of an imbalance of autoantibodies against G protein-coupled receptors (GPCR) in some autoimmune diseases, post-COVID syndrome, SBIs allowed researchers to assume the novel mechanism in these conditions - autoimmune autonomic nervous system imbalance. In this review, all data published on an imbalance of autoantibodies against GPCR, clinical symptoms and pathogenic mechanisms in CFS, Fibromyalgia, SBIs, COVID and PCS, SBS, POTS, and some autoimmune diseases were analyzed. Possible criteria to diagnose the autoimmune autonomic nervous system imbalance were created.

Fibromyalgia: one year in review 2022.

Fibromyalgia syndrome (FM) is a chronic widespread pain syndrome characterised by fatigue, sleep disturbances and many idiopathic pain symptoms. The aim of this review is to describe and summarise the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of fibromyalgia syndrome published between January 2021 and January 2022 and appearing on PubMed database. In particular, last year's literature focused on the impact of COVID-19 pandemic on FM patients, on new aetiopathogenetic horizons and the last conclusions about pharmacological and non-pharmacological interventions.

Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study.

BACKGROUND: Fibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration. MATERIALS AND METHODS: We conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck's depression inventory were also studied. RESULTS: A significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method. CONCLUSION: A three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.

Impact of a mid-urethral synthetic mesh sling on long-term risk of systemic conditions in women with stress urinary incontinence: a national cohort study.

OBJECTIVE: To compare the incidence of systemic conditions between women who had surgical treatment for stress incontinence with mesh and without mesh. DESIGN: National cohort study. SETTING: English National Health Service. POPULATION: Women with no previous record of systemic disease who had first-time urinary incontinence surgery between 1 January 2006 and 31 December 2013, followed up to the earliest of 10 years or 31 March 2019. METHODS: Competing-risks regression was used to estimate hazard ratios (HR), adjusted for patient characteristics, with HR > 1 indicating increased incidence following mesh surgery. MAIN OUTCOME MEASURES: First postoperative admission with a record of autoimmune disease, fibromyalgia or myalgic encephalomyelitis up to 10 years following the first incontinence procedure. RESULTS: The cohort included 88 947 women who had mesh surgery and 3389 women who had non-mesh surgery. Both treatment groups were similar with respect to age, socio-economic deprivation, comorbidity and ethnicity. The 10-year cumulative incidence of autoimmune disease, fibromyalgia or myalgic encephalomyelitis was 8.1% (95% CI 7.9-8.3%) in the mesh group and 9.0% (95% CI 8.0-10.1%) in the non-mesh group (adjusted HR 0.89, 95% CI 0.79-1.01; P = 0.07). A sensitivity analysis including only autoimmune diseases as an outcome returned a similar result. CONCLUSIONS: These findings do not support claims that synthetic mesh slings cause systemic disease. TWEETABLE ABSTRACT: No evidence of increased risk of systemic conditions after stress incontinence treatment with a mesh sling.

Evaluating the risk of QTc prolongation associated with hydroxychloroquine use with antidepressants in lupus patients with fibromyalgia.

OBJECTIVE: Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE) due to its immunomodulatory properties. Antidepressants are commonly used in patients with fibromyalgia syndrome (FMS). Both HCQ and antidepressants are reported to cause QTc prolongation, which potentially increases the risk for a lethal ventricular arrhythmia that can result in sudden death. The objective of the study is to investigate the risk of QTc prolongation associated with HCQ use concomitantly with antidepressants in lupus patients with FMS. METHODS: Outpatient 12-lead electrocardiograms (ECGs) were extracted from an electronic medical record and QTc intervals were calculated using the Bazett's formula. QTc intervals in 135 lupus patients treated with HCQ with or without antidepressants were analyzed. RESULTS: We found taking HCQ was associated with mild QTc prolongation, and the prolongation was not affected by the length of time of HCQ use or the accumulated dose of HCQ. Concurrent use of HCQ and antidepressants had not further increased QTc intervals in this cohort. However, four patients on HCQ alone and three patients on HCQ and antidepressants were found QTc interval more than 500 milliseconds and most of these patients had underlying cardiological conditions. CONCLUSIONS: It is important to evaluate lupus patient with ECG before and after starting HCQ, though our study suggests that while HCQ use did prolong the QTc in some, but the overall prolongation was subclinical, with or without antidepressants. ECG monitoring therefore is essential to identify new changes potentially related to drug use.

Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway.

Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague-Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia.

Passive transfer of fibromyalgia symptoms from patients to mice.

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

Could ferritin, vitamin B12, and vitamin D play a role in the etiopathogenesis of fibromyalgia syndrome?

Introduction. Fibromyalgia syndrome (FS) comprises general body pain, sleep disturbances, and fatigue. Vitamin B12 (VB), vitamin D (VD), and iron deficiencies lead to similar complaints. First, this study aimed to evaluate the VB, VD, and ferritin levels of patients with FS. Second, it aimed to investigate whether there was a relationship between these parameters and FS severity. Material and methods. The study included 58 female patients with FS and 58 healthy females as a control group. The patients completed the Fibromyalgia Impact Questionnaire (FIQ), Visual Analog Scale (VAS), fatigue questionnaire, Pittsburgh sleep quality scale, and the Short Form-36 (SF-36). This study examined the VD, VB, and ferritin levels of the patient and control groups. Results. The VB (240.0 [110.0-394.0] vs 291.0 [210.0-609.0] pg/ml, p<0.001), VD (12.5 [3.0-45.0] vs 20.0 [5.0-54.0] ng/ml, p=0.013), and ferritin levels (21.2 [4.0-86.0] vs 32.0 [7.1-120.0], ng/ml, p=0.009) of the FS patients were determined to be significantly lower than those of the control group. A negative correlation was determined between the number of tender points and VB, VD, and ferritin levels. In the regression analysis, we found low ferritin levels (odds ratio [OR] 1.036, 95% confidence interval [CI] 1.015-1.058, p<0.001) and VB (OR 1.010, CI 1.002-1.018, p=0.010) to be an independent risk factor for FS. Conclusions. There may be a relationship between VB, VD, and ferritin levels and the number of tender points in patients with FS. Levels of iron and VB may play a vital role in FS etiopathogenesis. However, VD levels may not be a risk factor for FS etiopathogenesis.

Nociplastic pain: towards an understanding of prevalent pain conditions.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update.

Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms.

Cationic liposome-encapsulated carotenoids as a potential treatment for fibromyalgia in an animal model.

The present study investigated the efficacy of cationic liposome-encapsulated carotenoids (lutein or beta-carotene) as a treatment in an animal model of fibromyalgia (FM). Preparation and characterization of the nano-sized cationic liposomal carotenoids have been carried out. FM has been induced in the experimental animals via successive subcutaneous reserpine injection (1 mg/kg). Animals were divided into four groups; control, reserpinized (Res), reserpinized and cationic liposomal lutein-treated (Res + CL-Lut), and reserpinized and liposomal beta-carotene-treated (Res + CL-Bc). Levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT), and oxidative stress markers (MDA, H2O2, NO, and GSH) were determined in the brain's cortical tissue of the different groups of animals. Furthermore, the spectral analysis of the electrocorticogram (ECoG) was carried out. Animal behavior was tested for different animal groups. Results showed a significant reduction in monoamines, an elevation of oxidative stress markers, a shift in the ECoG frequency band power, and a change in pain threshold of the reserpinized animals. A return to a non-significant difference from the control values of all the measured parameters has been obtained after two weeks of cationic liposomal carotenoid preparations treatment. The present findings shed more light on the validity of the reserpine model of FM and provide evidence for the antidepressant, antioxidant, and anti-nociceptive potential of the cationic liposomal carotenoids. The present results proofed that the natural product preparations on a nano-sized scale could be a good alternative to the pharmacological interventions for FM treatment.

Juvenile primary Fibromyalgia Syndrome: epidemiology, etiology, pathogenesis, clinical manifestations and diagnosis.

Juvenile primary fibromyalgia syndrome (JPFS) is a chronic, musculoskeletal pain syndrome affecting children and adolescents, most commonly adolescent girls. The syndrome has a multifactorial etiology, with altered central pain processing playing an important role. The hallmark symptom is severe, widespread musculoskeletal pain. Other symptoms include sleep and mood disturbances, headaches, stiffness, and subjective joint swelling. Physical examination can reveal multiple tender points. The diagnosis is clinical, with defined criteria. Early diagnosis and intervention are important. In this part of the review, we discuss the epidemiology, etiology, pathogenesis, clinical manifestations and diagnosis of JPFS. Part two will focus on treatment and prognosis.