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.

Functional Connectivity and Structural Signatures of the Visual Cortical System in Fibromyalgia: A Magnetic Resonance Imaging Study.

OBJECTIVE: Abnormal functional connectivity (FC) and structure in the brain are found in patients with fibromyalgia (FM). This study investigated FC and structural alterations of the visual cortical system, the emerging contributor to pain processing, in patients with FM. METHODS: Thirty pain-free participants and 26 patients with FM were enrolled. Clinical characteristics were evaluated using standardized scales. Structural and resting-state functional magnetic resonance imaging were conducted. Seed-based FC analyses, voxel-based morphometry, and surface-based morphometry were performed. The FC and cortical structure of the visual system were compared between the 2 groups. The correlation between functional and structural changes in the visual cortical system with clinical presentation in the FM group was analyzed. RESULTS: The patients with FM showed increased FCs within visual networks, of which the FC between the visual medial network and the right lingual gyrus (LG) was positively correlated with the Fibromyalgia Impact Questionnaire (FIQ) score. However, the FM group showed decreased FCs from the visual occipital network (VON) to several regions, of which the FCs from the VON to the bilateral frontal orbital cortices were negatively correlated with the FIQ and Pittsburgh Sleep Quality Index scores. Cortical thickness of the lateral occipital cortex, LG, and pericalcarine in FM tended to increase. CONCLUSION: Altered FCs and structure in the visual cortical system might be involved in the pathomechanisms and clinical presentation in FM. These findings could potentially support further studies that seek to find diagnostic methods and mechanism-based therapies in patients with FM.

AKAP12 and RNF11 as Diagnostic Markers of Fibromyalgia and Their Correlation with Immune Infiltration.

Fibromyalgia (FM) is a chronic nonarticular rheumatic disease mainly characterized by diffuse disseminated skeletal muscle pain, with varied symptoms including anxiety, sleep disturbance, and fatigue. Due to its unknown etiology and pathogenesis, FM is easily ignored in clinical practice, resulting in unclear diagnosis and difficult treatment. This study is aimed at investigating whether AKAP12 and RNF11 can be used as biomarkers for the diagnosis of FM and at determining their correlation with immune infiltration. The FM dataset in Gene Expression Omnibus (GEO) database was downloaded and was randomly divided into the training and test sets. Differentially expressed genes (DEGs) were screened, and functional correlation analysis was performed. Diagnostic markers of FM were screened and validated by random forest (RF). The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was then used to evaluate immune cell infiltration in the FM patients' peripheral blood. Finally, Spearman's rank correlation analysis was used to identify correlation between the diagnostic indexes and immune cell infiltration. A total of 69 DEGs were selected. Results indicated that AKAP12 and RNF11 can be used as diagnostic markers of FM, and CD8 + T cells might contribute in the pathogenesis of FM. In addition, AKAP12 was positively correlated with CD8 + T cells, while RNF11 was negatively correlated with CD8 + T cells. In conclusion, AKAP12 and RNF11 can be used as diagnostic indicators of FM, and CD8 + T cells may be involved in the occurrence and development of FM.

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.

CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement.

We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case-control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.

Scoping review and interpretation of myofascial pain/fibromyalgia syndrome: An attempt to assemble a medical puzzle.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common, overlooked, and underdiagnosed condition and has significant burden. MPS is often dismissed by clinicians while patients remain in pain for years. MPS can evolve into fibromyalgia, however, effective treatments for both are lacking due to absence of a clear mechanism. Many studies focus on central sensitization. Therefore, the purpose of this scoping review is to systematically search cross-disciplinary empirical studies of MPS, focusing on mechanical aspects, and suggest an organic mechanism explaining how it might evolve into fibromyalgia. Hopefully, it will advance our understanding of this disease. METHODS: Systematically searched multiple phrases in MEDLINE, EMBASE, COCHRANE, PEDro, and medRxiv, majority with no time limit. Inclusion/exclusion based on title and abstract, then full text inspection. Additional literature added on relevant side topics. Review follows PRISMA-ScR guidelines. PROSPERO yet to adapt registration for scoping reviews. FINDINGS: 799 records included. Fascia can adapt to various states by reversibly changing biomechanical and physical properties. Trigger points, tension, and pain are a hallmark of MPS. Myofibroblasts play a role in sustained myofascial tension. Tension can propagate in fascia, possibly supporting a tensegrity framework. Movement and mechanical interventions treat and prevent MPS, while living sedentarily predisposes to MPS and recurrence. CONCLUSIONS: MPS can be seen as a pathological state of imbalance in a natural process; manifesting from the inherent properties of the fascia, triggered by a disrupted biomechanical interplay. MPS might evolve into fibromyalgia through deranged myofibroblasts in connective tissue ("fascial armoring"). Movement is an underemployed requisite in modern lifestyle. Lifestyle is linked to pain and suffering. The mechanism of needling is suggested to be more mechanical than currently thought. A "global percutaneous needle fasciotomy" that respects tensegrity principles may treat MPS/fibromyalgia more effectively. "Functional-somatic syndromes" can be seen as one entity (myofibroblast-generated-tensegrity-tension), sharing a common rheuma-psycho-neurological mechanism.

Prognostic factors of trochanteric bursitis in surgical-staged patients: a prospective study.

BACKGROUND: Trochanteric bursitis or greater trochanteric pain syndrome is a common disorder and frequent cause of lateral hip pain. It can lead to severe functional impairment with increase morbidity and poor quality of life.The purpose of the current study was to identify and evaluate relationship between health-related factors, as prognostic indicators, and clinical outcomes. METHODS: A single-centre, prospective study was conducted and 60 patients (62 hips) were included with a minimum 12 months of follow-up. Clinical outcomes were evaluated using Hip Outcome Scale, Single Assessment Numeric Evaluation and Visual Analogue Scale. Radiological assessments and health-related factors were documented in an attempt to understand their validity as predictors of clinical outcomes. Complications and recurrence rates were also analyzed. RESULTS: Univariate model revealed that an increased BMI (p = 0.001; OR = 1.05; 95% CI, 1.02-1.07); number of previous corticosteroid infiltrations (p = 0.001; OR = 1.28, 95% CI, 1.11-1.48); longer time from symptom onset to surgery (p = 0.001; OR = 1.19; 95% CI, 1.12-1.28); smoker status (p = 0.001; OR 11.2; 95% CI, 3.30-44.2); and the presence of prior lumbosacral fusion (LSF) (p = 0.001; OR 13.8; 95% CI, 2.96-101); were prognostic factors predisposing for poor clinical outcomes.Among prognostic health-related factors were medical comorbidities such as emotional distress (p < 0.001; OR 26.1; 95% CI, 5.71-192); fibromyalgia (p = 0.026; OR 3.56; 95% CI, 1.16-11.7); and hyporthyroidism (p = 0.005, OR = 6.55, 95% CI, 1.73-28.7). CONCLUSIONS: Better overall physical function was predicted by lower number of corticosteroid infiltrations, shorter time span from symptom onset to surgery, non-smoker status and the absence of prior lumbosacral fusion. Obesity, smoking, the presence of emotional distress, fibromyalgia and hypothyroidism seem to increase the risk of poor clinical outcomes. A proper selection and/or correction of modifiable prognostic factors could reduce the incidence of endoscopic treatment failure and, as a consequence, improve patient outcomes and quality of life. However, future efforts should focus on experimental and randomised studies to fully determine these associations.

Right anterior insula is associated with pain generalization in patients with fibromyalgia.

ABSTRACT: Despite diffuse tenderness, patients with fibromyalgia (FM) have reported a wide range of areas with musculoskeletal pain. This study investigated the neural structures and neuroanatomical networks associated with self-reported widespread pain in FM using magnetic resonance imaging. We collected clinical profiles and brain magnetic resonance imaging data of newly diagnosed patients with FM. A total of 138 patients with FM were divided into 3 subgroups based on the number of pain areas, with 3 to 8, 9 to 12, and 13 to 19 areas, respectively. Using voxel-based morphometry analysis, we first identified the neural structure that showed a trend of volumetric change across the 3 subgroups. We then used it as a candidate seed of interest with a seed-to-voxel analytical approach to explore the structural covariance (SC) networks of the whole brain. Finally, we studied the trend of changes in the distribution and strength of SC networks across subgroups of patients. We found a decreasing trend in the volumes of the right anterior insular cortex (rAIC) across the 3 subgroups that had an increased number of pain areas. An increasing trend in the number of neural substrates over the subcortical regions, especially the basal ganglion, showed SC to the rAIC, and a decreasing trend of SC strength was shown between the rAIC and the precuneus, frontal cortex, anterior and posterior cingulate, and lingual gyri, across the patient subgroups with increased pain areas. The rAIC and its altered connection with specific brain regions indicates widespread pain in patients with FM.

Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior.

Modulation of hippocampal dentate gyrus (DG) excitability regulates anxiety. In the DG, glutamatergic mossy cells (MCs) receive the excitatory drive from principal granule cells (GCs) and mediate the feedback excitation and inhibition of GCs. However, the circuit mechanism by which MCs regulate anxiety-related information routing through hippocampal circuits remains unclear. Moreover, the correlation between MC activity and anxiety states is unclear. In this study, we first demonstrate, by means of calcium fiber photometry, that MC activity in the ventral hippocampus (vHPC) of mice increases while they explore anxiogenic environments. Next, juxtacellular recordings reveal that optogenetic activation of MCs preferentially recruits GABAergic neurons, thereby suppressing GCs and ventral CA1 neurons. Finally, chemogenetic excitation of MCs in the vHPC reduces avoidance behaviors in both healthy and anxious mice. These results not only indicate an anxiolytic role of MCs but also suggest that MCs may be a potential therapeutic target for anxiety disorders.

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.

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. [...].

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.

Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic D2/D3 Receptor Agonist, Ropinirole, Attenuate Fibromyalgia-Like Symptoms in Mice.

Fibromyalgia is a disease characterized by lowered pain threshold, mood disorders, and decreased muscular strength. It results from a complex dysfunction of the nervous system and due to unknown etiology, its diagnosis, treatment, and prevention are a serious challenge for contemporary medicine. Impaired serotonergic and dopaminergic neurotransmission are regarded as key factors contributing to fibromyalgia. The present research assessed the effect of serotonergic and dopaminergic system modulators (vortioxetine and ropinirole, respectively) on the pain threshold, depressive-like behavior, anxiety, and motor functions of mice with fibromyalgia-like symptoms induced by subcutaneous reserpine (0.25 mg/kg). By depleting serotonin and dopamine in the mouse brain, reserpine induced symptoms of human fibromyalgia. Intraperitoneal administration of vortioxetine and ropinirole at the dose of 10 mg/kg alleviated tactile allodynia. At 5 and 10 mg/kg ropinirole showed antidepressant-like properties, while vortioxetine had anxiolytic-like properties. None of these drugs influenced muscle strength but reserpine reduced locomotor activity of mice. Concluding, in the mouse model of fibromyalgia vortioxetine and ropinirole markedly reduced pain. These drugs affected emotional processes of mice in a distinct manner. Hence, these two repurposed drugs should be considered as potential drug candidates for fibromyalgia. The selection of a specific drug should depend on patient's key 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.

Functional characterization of nociceptive mechanisms involved in fibromyalgia and electroacupuncture.

The diagnosis and treatment of chronic pain in diseases such as fibromyalgia (FM) are lacking effective standardised protocols that can be widely accessed and implemented by healthcare professionals across the globe. Persistent hyperalgesia and allodynia are characteristic symptoms of FM. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. We examined the contribution of the transient receptor potential vanilloid 1 (TRPV1) channel and the major nociceptive components in response to fibromyalgia-like pain in an intermittent cold-stress (ICS) model, in the prefrontal cortex, somatosensory cortex, hippocampus and thalamus areas of the brain. The use of TRPV1 gene deletion mice served to elucidate the role of the TRPV1 receptor in the development and expression of FM-like pain. The results suggest that TRPV1 upregulation is central to the sustained sensation of FM related hyperalgesia. Furthermore, the potential therapeutic benefits of electroacupuncture (EA) at bilateral ST36 acupoint were analysed in order to identify the analgesic effects and mechanism associated with this therapy. The findings indicate that EA treatment successfully attenuated both mechanical and thermal hyperalgesia and suggests that a definitive underlying mechanism of neuromodulation through EA is responsible for providing analgesic benefits to patients suffering from FM.

[Production of knowledge using data collected by associations of patients: The fibromyalgia example]. / Production de savoirs à partir de données collectées par les associations de malades - L'exemple de la fibromyalgie.

To respond to the social challenge of medical knowledge democratisation, numerous initiatives have been developed: information, training or consultation of patients or research applications funded by associations of patients. Only a few numbers of collaborations are initiated by the persons directly involved (patients and relatives) or fulfill association research need. We have adopted and tested such an approach with the French fibromyalgia association (Fibromyalgie France). Our work demonstrates the interest to use data collected by associations of patients to answer to their questioning or to rise further relevant research questions. Such participative approach will have a pertinent and significant impact on the knowledge of diseases and on the development of collaborative actions of research, providing a better answer to patient needs, while being methodologically rigorous.

TITLE: Production de savoirs à partir de données collectées par les associations de malades - L'exemple de la fibromyalgie. ABSTRACT: Pour répondre au défi sociétal de démocratisation de l'accès à la connaissance, différentes initiatives de recherches participatives se développent : actions d'information, de formation ou de consultation des citoyens ou par l'intermédiaire de demandes de financement par des chercheurs auprès des associations. Cependant, peu des collaborations chercheurs-malades sont à l'initiative des personnes concernées, les patients et leurs familles. Nous avons adopté et testé cette démarche à la demande et en coopération avec l'association Fibromyalgie France.

The impact of coexisting fibromyalgia syndrome on disease activity in patients with psoriatic arthritis and rheumatoid arthritis: A cross-sectional study.

BACKGROUND/OBJECTIVE: This study aims to assess the coexistence of fibromyalgia syndrome (FMS) and impact of possible FMS on disease activity in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: A total of 126 patients, aged 18-65 years old, who were being followed up with PsA (n = 64) and RA (n = 62) diagnoses were included. The Fibromyalgia Rapid Screening Tool (FiRST) was administered for screening FMS. Patients were divided according to the presence of FMS; PsA patients with FMS, patients with PsA without FMS, patients with both RA and FMS and patients with RA without FMS. Disease Activity Score 28 (DAS28) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were recorded. RESULTS: FMS was detected in 26.5% of the patients with PsA and 17.7% of the patients with RA (p = .04). A statistically significant higher DAS28 and BASDAI scores were found in patients with FMS (p < .05). There was statistically significant correlation between FiRST with DAS28 and BASDAI scores (p < .001, p = .03, respectively) in PsA patients. No significant correlation was found between FiRST score with age, disease duration, CRP and DAS28 in patients with RA (p > .05). CONCLUSION: The patients with concomitant FMS had higher disease activity parameters (DAS28 and BASDAI) than those without FMS.

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.

Investigation of ACE rs4646994, MTHFR rs1801133 and VDR rs2228570 Genotypes in Jordanian Patients with Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread body pain, weakness in certain parts of the body (critical points), low pain tolerance, sleep disturbances, and fatigue. This syndrome is considered rare in Jordan. OBJECTIVES: The research aimed to find out the association of the angiotensin converting enzyme, methylenetetrahydrofolate reductase, and vitamin D receptor (ACE, MHFTR, and VDR, respectively) genotypes with FMS among Jordanian patients. METHODS: This work included 22 FM patients and 22 healthy individuals of Jordanian Arabic origin. The ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 genotypes were determined using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism. RESULTS: No associations between ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 with the vulnerability of a person for the development of FMS were found. However, we found an association between the ACE rs4646994 genotype and restless leg among FM patients. CONCLUSION: Based on the result from this study, it appears that the ACE rs4646994 genotype is associated with restless leg among FMS patients of Jordanian origin. Further clinical investigations with larger sample sizes are required to confirm these findings and understand the molecular mechanism of ACE rs4646994 genetic variant in the restless leg syndrome among FM patients.