Reduced sympathetic activity is associated with the development of pain and muscle atrophy in a female rat model of fibromyalgia.

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.

Adrenalectomy attenuates hyperalgesia but does not regulate muscle wasting in a female rat model of fibromyalgia.

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.

A behavioral and brain imaging dataset with focus on emotion regulation of women with fibromyalgia.

Fibromyalgia is a chronic condition characterized by widespread pain, as well as numerous symptoms related to central sensitization such as: fatigue, cognitive disturbances, constipation/diarrhea and sensory hypersensitivity. Furthermore, depression and anxiety are prevalent comorbidities, accompanied by emotion processing and regulation difficulties. Although fibromyalgia physiopathology is still not fully understood, neuroimaging research methods have shown brain structural and functional alterations as well as neuroinflammation abnormalities. We believe that open access to data may help fibromyalgia research advance more. Here, we present an open dataset of 33 fibromyalgia female patients and 33 paired healthy controls recruited from a Mexican population. Dataset includes demographic, clinical, behavioural and magnetic resonance imaging (MRI) data. The MRI data consists of: structural (T1- and T2- weighted) and functional (task-based and resting state) sequences. The task was an emotion processing and regulation task based on visual stimuli. The MRI data contained in the repository are unprocessed, presented in Brain Imaging Data Structure (BIDS) format and available on the OpenNeuro platform for future analysis.

Comment on Siracusa et al. Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int. J. Mol. Sci. 2021, 22, 3891.

We have read the study by Siracusa et al. [...].

The mapping of cortical activation by near-infrared spectroscopy might be a biomarker related to the severity of fibromyalgia symptoms.

The delta value of oxyhemoglobin (Δ-HbO) determined by functional near-infrared spectroscopy at prefrontal cortex (PFC) and motor cortex (MC) based on primary (25 °C) and secondary (5 °C) thermal stimuli presented a larger peak latency at left MC in fibromyalgia than in controls. The difference between HbO concentration 15 s after the thermal stimuli ending and HbO concentration before the thermal stimuli onset (Δ-HbO*) at left PFC increased 47.82% in fibromyalgia and 76.66% in controls. This value had satisfactory discriminatory properties to differentiate cortical activation in fibromyalgia versus controls. A receiver operator characteristics (ROC) analysis showed the Δ-HbO* cutoffs of - 0.175 at left PFC and - 0.205 at right PFC offer sensitivity and specificity of at least 80% in screening fibromyalgia from controls. In fibromyalgia, a ROC analysis showed that these cutoffs could discriminate those with higher disability due to pain and more severe central sensitization symptoms (CSS). The ROC with the best discriminatory profile was the CSS score with the Δ-HbO* at left PFC (area under the curve = 0.82, 95% confidence interval = 0.61-100). These results indicate that cortical activation based on Δ-HbO* at left PFC might be a sensitive marker to identify fibromyalgia subjects with more severe clinical symptoms.

Pool-based exercise for amelioration of pain in adults with fibromyalgia syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of pool-based exercises on pain symptomatology among adults with fibromyalgia syndrome. METHODS: A systematic review and meta-analysis were carried out using PRISMA guidelines. Database search was conducted by two independent reviewers. For meta-analysis, the visual analogue scale (VAS) score for pain was used as the primary outcome and the Fibromyalgia Impact Questionnaire (FIQ) score was utilized as the secondary outcome. RESULTS: A total of 42 out of 292 potentially eligible studies were selected for being read in full by reviewers, 14 of which were included in meta-analysis, being 10 of them used in sensitivity analysis of either the primary or secondary outcome. Data pooled from 10 randomized controlled trials (n = 508) revealed that patients who underwent pool-based exercises exhibited a significantly lower mean in VAS score as compared to controls (SMD = -0.27, 95% CI: -0.45 to -0.09). Regarding FIQ scores, data from 10 randomized controlled trials were pooled (n = 578) and a lower mean score was also shown in the group that underwent a pool-based exercise program (SMD = -0.29, 95% CI: -0.49 to -0.09). Limitations of this study include the small sample size and moderate dropout rates in currently available clinical trials. CONCLUSION: Pool-based exercise may provide some additional benefit for pain relief in adults with fibromyalgia as compared to either land-based or no physical exercise. IMPLICATIONS OF KEY FINDINGS: Collectively, these findings suggest that pool-based exercise deserves further attention as a potential adjuvant therapeutic option for adults with fibromyalgia. PROSPERO registration number: CRD42019136755.

Relevance of Mitochondrial Dysfunction in the Reserpine-Induced Experimental Fibromyalgia Model.

Fibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitochondrial modulators. Reserpine (1 mg/kg) was subcutaneously injected once daily for three consecutive days in male Swiss mice. We carried out analyses of reserpine-induced FM-related symptoms, and their modulation by using mitochondrial insult on ATP synthesis (oligomycin; 1 mg/kg, intraperitoneally) or mitochondrial protection (coenzyme Q10; 150 mg/kg/5 days, orally). We also evaluated the effect of reserpine on mitochondrial function using high-resolution respirometry and oxidative status. Reserpine caused nociception, loss in muscle strength, and anxiety- and depressive-like behaviours in mice that were consistent with clinical symptoms of FM, without inducing body weight and temperature alterations or motor impairment. Reserpine-induced FM-related symptoms were increased by oligomycin and reduced by coenzyme Q10 treatment. Reserpine caused mitochondrial dysfunction by negatively modulating the electron transport system and mitochondrial respiration (ATP synthesis) mainly in oxidative muscles and the spinal cord. These results support the role of mitochondria in mediating oxidative stress and FM symptoms in this model. In this way, reserpine-inducing mitochondrial dysfunction and increased production of ROI contribute to the development and maintenance of nociceptive, fatigue, and depressive-like behaviours.

Massage therapy in cortisol circadian rhythm, pain intensity, perceived stress index and quality of life of fibromyalgia syndrome patients.

We investigate the effects of a massage therapy program (MTP) in cortisol concentration (CC), intensity of pain, quality of life and perceived stress index of fibromyalgia patients. Volunteers (n = 24, aged 26-55 years) were treated with MT, twice a week for three months. They answered the Fibromyalgia Impact Questionnaire (FIQ), Perceived Stress Questionnaire (PSQ) and McGill Pain Questionnaire (MPQ-Br), and collected saliva to evaluate CC before and after the end of each month. The MT had improvement in quality of life, according to the FIQ results, and promoted reduction in PSQ values after the second (PSQ2-0.62 ± 0.04vsPSQ0-0.71 ± 0.04) and third month (PSQ3-0.64 ± 0.04vsPSQ0-0.71 ± 0.04). The MTP also promoted reduction in pain after the third month (MQP-Br1-44.50 ± 2.15vsMQP-Br4-35.38 ± 3.71). Despite PSQ reduction, the CC were not affected by the program. This pilot suggests that this treatment improved quality of life, reduced perceived stress index and pain in these volunteers.

Pacientes com fibromialgia atendidos no Ambulatório de Dor da Unifesp / Fibromyalgia patients attended in the outpatients Pain Sector of Federal University of São Paulo

Foi feita análise de prontuários de pacientes com fibromialgia atendidos no Setor de Dor da Unifesp no período de um ano, anotando dados, como idade, sexo, estado civil, ocupação, outras síndromes dolorosas associadas e tratamentos.

As possíveis fontes fisiopatológicas da fibromialgia e suas importâncias como alvos para tratamento / The possible physiopathological sources of fibromyalgia and its importance as targets for treatment

A fibromialgia é uma síndrome caracterizada por dor difusa, fadiga e alterações do sono, além de diversos outros sintomas. Sua fisiopatologia permanece desconhecida, porém existem diversas hipóteses acerca de sua origem.Inicialmente, discute-se a teoria da somatização, que tem como base a ocorrência de comorbidades com agravos psicológicos e psiquiátricos, tais como traumas e abusos na infância e síndrome do estresse pós-traumático. Posteriormente, discorre-se sobre a hipótese neurológica, baseada em alterações de fluxo e ativação cerebral encontradas em métodos diagnóstico de imagem é revista a teoria neuroendócrina, fundamentada em alterações dos níveis hormonais e de neurotransmissores a hipótese inflamatória, que se apoia em níveis alterados de citocinas plasmáticas e de biópsias de pele e, por fim, as alterações receptoriais que residem em um número alterado dos receptores NMDA, relevantes no processo de alodinia, evidencia-se a possível importância destas hipóteses como base terapêutica.

[Quality of life in multiple sclerosis and other chronic autoimmune and non-autoimmune diseases]. / Calidad de vida en esclerosis multiple y otras enfermedades cronicas autoinmunes y no autoinmunes.

INTRODUCTION: Diseases that involve the nervous system and the musculoskeletal system are particularly likely to produce different limitations and deficits, and to affect the individual conception of quality of life. AIM: To determine the impact on quality of life generated by chronic autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), ankylosing spondylitis (AS) and chronic musculotendinous diseases like osteoarthritis (OA) and fibromyalgia (FM), using the Short Form 36-item (SF-36) health questionnaire. PATIENTS AND METHODS: A descriptive cross-sectional study was conducted between January 2004 and June 2006 and included 509 individuals, of whom 56 had MS, 36 SS, 24 AS, 200 RA, 65 SLE, 54 OA and 74 FM. Guided interviews were conducted to evaluate each sphere of the SF-36 health questionnaire. The statistical analysis was performed using the general lineal model, with means differences according to each diagnosis. RESULTS: Compared to patients with RA, those with MS showed significant differences in the physical functioning and social functioning dimensions. The lowest score was recorded in those with FM, except in physical functioning, where MS had the lowest mean. No differences were found in the mean scores on general conception of the state of health in each condition analysed. CONCLUSIONS: Different neurological functions deteriorate progressively in MS, which has repercussions on the musculoskeletal system; this leads to a poorer quality of life, mainly in the physical and social functions. The disability generated is not only defined by deficit but also by the degrees of functional limitation within the context of personal health. Quality of life thus becomes a global biopsychosocial phenomenon.

[Salivary gland scintigraphy en Sjogren syndrome and its relation with the result of lip biopsy. Comparative study with a control population]. / Utilidad de la cintigrafía de glándulas salivales en el síndrome de Sjögren y su relación con el resultado de la biopsia de labio. Estudio comparativo con una población control.

BACKGROUND: Salivary gland scintigraphy allows a non invasive, morphological and functional assessment of parotid and submaxillary salivary glands. AIM: To describe the main features of salivary gland scintigraphy in patients with Sjögren syndrome, rheumatic fibromyalgia and normal controls and compare the results with lip biopsy. PATIENTS AND METHODS: Sixty one normal controls, 66 patients with Sjögren syndrome and 18 patients with rheumatic fibromyalgia were studied. For the diagnosis of Sjögren syndrome and fibromyalgia rheumatica, the Modified European and American College of Rheumatology criteria were used, respectively. Lip biopsies were obtained in 52 patients with Sjögren syndrome. Scintigraphy was done with a gamma camera and computer after the administration of 99mTc-pertechnetate, obtaining images during 30 min and creating time/activity curves. Scintigraphy was classified as normal, with mild or severe alterations. RESULTS: Scintigraphy was normal in 74% of control subjects and in 26%, it had mild alterations. In 72% of patients with rheumatic fibromyalgia, scintigraphy was normal whereas in 28%, it had mild alterations. In 27% of patients with Sjögren syndrome, scintigraphy was normal, in 27% it had mild alterations and in 46%, severe alterations. There was a positive and significant correlation between pathological alterations of salivary glands and scintigraphic alterations (r = 0.642, p < 0.001). CONCLUSIONS: Severe scintigraphic alterations of salivary glands strongly support the diagnosis of Sjögren syndrome. Mild alterations are non specific and a normal scintigraphy does not exclude the diagnosis.

Fibromialgia: revisión de los aspectos clínicos y diagnósticos / Fibromyalgia: review of the clinical aspects

El objetivo de este artículo es revisar las principales características clínicas, criterios diagnósticos y métodos de acompañamiento clínico de la fibromialgia. Los autores presentan también una breve revisión histórica de los conocimientos de este síndrome y comenta la necesidad de divulgación de los conocimientos adquiridos para realizar un diagnóstico precoz y mejorar la calidad de vida de los pacientes

Rheumatic manifestations of neurologic and psychiatric diseases.

Rheumatic diseases have not proved to be more prevalent among neurologic or psychiatric patients than in the general population, except for osteoarthritis in some chronic disabling neurologic conditions (poliomyelitis, spinal cord injury). Some neurologic entities with relevant musculoskeletal manifestations are described here. The lower prevalence of rheumatoid arthritis in schizophrenia patients is mentioned, and a brief description is presented of somatoform disorders that may confound diagnosis with rheumatic diseases. Factitious disorders and malingering are frequently presented with rheumatic complaints such as low back pain and may have an important impact on the costs associated with the disease. Finally, some of the immune system abnormalities described in major depression and schizophrenia are mentioned with a clear reference to the growing field of psychoneuroimmunology. This paper will not address the issue of neurologic or psychiatric manifestations of rheumatic diseases.

Hereditary inflammatory vasculitis with persistent nodules. A genetically-determined new entity probably related to lupus erythematosus

A family of 3 generations is reported, in which several members had recurrent nodules over the limbs since early....