Pathophysiology Of Fibromyalgia Research Articles

Machine learning identifies fatigue as a key symptom of fibromyalgia reflected in tyrosine, purine, pyrimidine, and glutaminergic metabolism.

Fibromyalgia patients vary in clinical phenotype and treatment can be challenging. The pathophysiology of fibromyalgia is incompletely understood but appears to involve metabolic changes at rest or in response to stress. We enrolled 54 fibromyalgia patients and 31 healthy controls to this prospective study. Symptoms were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and blood samples were collected for metabolomics analysis at baseline and after an oral glucose tolerance test and a cardiopulmonary exercise test. We identified key symptoms of fibromyalgia and related them to changes in metabolic pathways with supervised and unsupervised machine learning methods. Algorithms trained with the FIQ information assigned the fibromyalgia diagnosis in new data with balanced accuracy of 88% while fatigue alone already provided the diagnosis with 86% accuracy. Supervised analyses reduced the metabolomic information from 77 to 13 key markers. With these metabolites, fibromyalgia could be identified in new cases with 79% accuracy. In addition, 5-hydroxyindole-3-acetic acid and glutamine levels correlated with the severity of fatigue. Patients differed from controls at baseline in tyrosine and purine pathways, and in the pyrimidine pathway after the stress challenges. Several key markers are involved in glutaminergic neurotransmission. This data-driven analysis highlights fatigue as a key symptom of fibromyalgia. Fibromyalgia is associated with metabolic changes which also reflect the degree of fatigue. Responses to metabolic and physical stresses result in a metabolic pattern that allows discrimination of fibromyalgia patients from controls and narrows the focus on key pathophysiological processes in fibromyalgia as treatment targets.

Identification of unique genomic signatures in patients with fibromyalgia and chronic pain

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain. The pathophysiology of fibromyalgia is not clearly understood and there are no specific biomarkers available for accurate diagnosis. Here we define genomic signatures using high throughput RNA sequencing on 96 fibromyalgia and 93 control cases. Our findings revealed three major fibromyalgia-associated expression signatures. The first group included 43 patients with a signature enriched for gene expression associated with extracellular matrix and downregulation of RhoGDI signaling pathway. The second group included 30 patients and showed a profound reduction in the expression of inflammatory mediators with an increased expression of genes involved in the CLEAR signaling pathway. These results suggest defective tissue homeostasis associated with the extra-cellular matrix and cellular program that regulates lysosomal biogenesis and participates in macromolecule clearance in fibromyalgia. The third group of 17 FM patients showed overexpression of pathways that control acute inflammation and dysfunction of the global transcriptional process. The result of this study indicates that FM is a heterogeneous and complex disease. Further elucidation of these pathways will lead to the development of accurate diagnostic markers, and effective therapeutic options for fibromyalgia.

Topological alterations in white matter structural networks in fibromyalgia.

Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM. This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated. Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected). The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM.

The crosstalk of the pathophysiologic models in fibromyalgia.

Fibromyalgia (FM) is a heterogeneous condition with various mechanisms (endotype) and manifestations (phenotypes). Many worthy endeavors have been dedicated to exploring the main trajectories of FM pathogenesis, depicted as the models of FM development. The Imbalance of Threat and Soothing Systems (FITSS) model, which is an advancing psychosocial form of the "central sensitization" model, and autonomic nervous system (ANS) model, besides new discoveries of potential pathways for FM development such as autoimmunity, small fiber pathology, and gut-brain axis currently comprise all our knowledge assets about FM pathogenesis. The pathophysiology of fibromyalgia is too complex to justify with one model, one main loop of pathogenesis, and one terminator. It appears that the variable FM models could justify some phenotypes of FM. Currently, our knowledge about FM pathogenesis and trying to match the different pathways and links mimic solving a puzzle in the hands of beginners. Until unraveling many missed interconnections and formulas between numerous scrambled pieces of the FM puzzle, proposing an integrated model seems not possible. This review focuses on the main trajectories of FM pathogenesis proposed thus far and tries to illuminate the crosstalking between them. We also propose the subgrouping FM into more homogenous categories based on the endotype-phenotype characteristics. It could provide a more pragmatic approach toward understanding of the diverse network of FM pathogenesis as well as the personalized stratification of FM. Key Points • The disentangled nature of FM pathogenesis escapes from embracing under one integrated model. • There appears to be no way for formulizing FM pathogenesis except the acknowledgment of the different pathways and their crosstalk explored as yet. • Acknowledging the different endotypes/phenotypes of FM spectrum and classifying them into more homogenous groups can help to the pragmatic approach to FM.

Oxidative stress may be a contributing factor in fibromyalgia patients' pain mechanisms.

The pathophysiology of fibromyalgia (FM), a continuously painful syndrome with no known origin, has been related to mitochondrial dysfunction, oxidative stress, and inflammation. Recent studies have shown that FM may be associated with an oxidative balance disorder. The objective of this study was to measure the levels of oxidative stress in FM patients and try to understand the association between FM and free radicals. This study was performed on 100 volunteers admitted to the University of Health Sciences, Sultan 2, Abdulhamid Han Health Application and Research Center Physical Therapy and Rehabilitation Clinic, including 50 healthy controls and 50 patients with FM. To analyze oxidative stress biomarkers, total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. Total thiol (TT) and native thiol (NT) concentrations were measured to determine the relationship between thiol groups. Disulfide (DIS) and oxidative stress index (OSI) were calculated with mathematical formulas. While TOS and OSI levels were statistically higher in FM patients, TAS levels were significantly lower compared to the healthy control group (p<0.001). In comparison to the healthy control group, FM patients had considerably decreased TT and NT levels. DIS levels were significantly higher in FM patients than in controls (p<0.001). Reactive oxygen species have several negative impacts on the human body. As a result of the measurements we analyzed, the relationship between FM and oxidative stress should be studied in terms of disease progression and may help improve the treatment process.

Benefits of the Light Consumption of Red Wine in Pain, Tender Points, and Anxiety in Women with Fibromyalgia: A Pilot Study.

Fibromyalgia (FM) is characterized by chronic widespread pain, as well as anxiety, sadness, and depression. These symptoms are present in most patients and have a negative impact on their daily, family, and social life. The role of neurotransmitters in the pathophysiology of FM has been extensively discussed. The scientific evidence shows that levels of serotonin are decreased in patients with FM. Numerous studies support the beneficial effects that moderate wine consumption has on the body, with cardiovascular, endocrine, bone, and muscle improvements. The objective of this pilot study was to assess whether light consumption of red wine improves the main symptoms of FM. The study consisted of an experimental study with a control group with a total of 60 women diagnosed with FM following the American College of Rheumatology's criteria. The experimental group ingested 15 g of alcohol per day, in the form of red wine, over a period of four weeks. The outcome measures were: the level of pain in tender points, sadness, anxiety, depression, and quality of life. The assessments tools were: tender point graphics, the visual analogue scale (for the assessment of pain and sadness), the Hamilton Anxiety Scale, the Hamilton Depression Rating Scale, and the Fibromyalgia Impact Questionnaire. The measurements were completed before and after the consumption of red wine. In addition, the differences between groups were evaluated in terms of drug consumption in the pre-intervention and follow-up phases. Statistically significant improvements were obtained in the wine ingestion group for the variables of pain (p = 0.038), tender points (p < 0.001), and anxiety (p = 0.028). An improvement in the mean values was observed in favor of the experimental group for the variables of sadness, depression, and quality of life. The differences observed in the changes seen in the groups that were in favor of the wine ingestion group should not be attributed to the consumption of drugs but to the fact that the experimental group had a light intake of red wine. The results of this pilot study suggest a potential relationship between alcohol intake through the light consumption of red wine as part of the patients' diet and the improvement of the main symptoms of fibromyalgia. Future studies are necessary to confirm these preliminary data; a bigger sample and a controlled diet should be considered, and the mechanisms through which improvements are achieved should be analyzed.

Fibromyalgia: one year in review 2023.

Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain that affects millions of people worldwide. This article discusses various aspects of FM described in scientific papers published in 2022 and indexed in the PubMed database, including the most recent diagnostic acquisitions (especially in relation to the juvenile form of FM), risk factors, co-morbidities and objective measures. Emphasis is placed on the importance of identifying FM early and improving diagnostic methods (e.g. physical measurements, including walking test performance, hand grip force, and autonomic tests). The article also considers hypotheses concerning the pathophysiology of FM, including the role of inflammation, gut dysbiosis, and neuroinflammation, and possible treatment options, including medications such as antioxidants and kinin antagonists, neurostimulation, and mind-body interventions. Although ketamine, vitamin D, and hormone therapy have shown promise in reducing FM symptoms, further research is needed to optimise their use. Neurostimulation techniques, such as transcutaneous electrical nerve stimulation, transcranial direct-current stimulation and transcranial magnetic stimulation, have been investigated in terms of their efficacy in reducing pain and improving the quality of life. Finally, the role of nutrition is discussed as study findings suggest that weight control, modified high-antioxidant diets, and nutritional supplementation can help to alleviate the symptoms of FM.

Association between Thyroid autoimmunity and Fibromyalgia: Single center retrospective study (P9-6.004)

<h3>Objective:</h3> The objective of this study was to describe the prevalence of anti TPO ab among FM patients, their thyroid status and to evaluate clinical response to corticosteroids. <h3>Background:</h3> Fibromyalgia (FM) is a disorder characterized by widespread musculoskeletal pain and other somatic symptoms. Studies have shown that there is a high prevalence of anti TPO ab (Thyroid peroxidase antibody) positivity among FM patients. It is unknown if thyroid autoimmunity is a predisposing factor for FM. <h3>Design/Methods:</h3> We included 107 patients who were diagnosed with FM based on 2010 American College of Rheumatology Criteria who attended our neurology clinic at Appusami Hospital, India between July 2019 and 2022. We recorded data including age, gender, thyroid profile, anti TPO titer [Negative (&lt;15), positive (15 to 500), strongly positive(&gt;500)] and calculated age adjusted odds ratio for steroid responsiveness. <h3>Results:</h3> Mean age of the study group was 48.29 and 78.5% were females. In our series, 75.7% of FM patients had positive anti TPO ab (Positive- 41.12%;strongly positive-35.51%). 51.40% were euthyroid, 38.32% were hypothyroid and 10.28% were hyperthyroid. Overall 56.8% responded well to steroids. (80.85% of strongly positive;19.15% of positive patients). Age-adjusted odds of steroid response in patients with higher anti TPO ab is 5.2 times that of the one with low ab (p&lt;0.001) (95%CI 3.03;9.04) <h3>Conclusions:</h3> Thyroid autoimmunity is frequently associated with middle aged women with FM. Higher anti TPO ab titers strongly correlated with steroid responsiveness in our study and we recommend a short course of steroids for this subset of patients. These findings need to be confirmed with a larger prospective study. Further research should focus on understanding the pathophysiology of FM and it9s the causal relationship with thyroid autoimmunity. <b>Disclosure:</b> Dr. Eswaradass has nothing to disclose. C Eswaradass, 303 has nothing to disclose. Dr. Thermalingem has nothing to disclose. Dr. Thirunavukkarasu has nothing to disclose. Dr. Gurunathan has nothing to disclose.

Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge

BackgroundThe pathophysiology of fibromyalgia (FM) is thought to include an overactive immune system, leading to central nervous system sensitization, allodynia, and hyperalgesia. We aimed to test this theory using an experimental immune system activation procedure and neuroimaging with magnetic resonance spectroscopic imaging (MRSI). MethodsTwelve women with FM and 13 healthy women (healthy controls; HC) received 0.3 or 0.4 ng/kg endotoxin and underwent MRSI before and after the infusion. Changes in brain levels of choline (CHO), myo-inositol (MI), N-Acetylaspartate (NAA), and MRSI-derived brain temperature were compared between groups and dosage levels using mixed analyses of variance. ResultsSignificant group-by-time interactions in brain temperature were found in the right thalamus. Post-hoc testing revealed that brain temperature increased by 0.55 °C in the right thalamus in FM (t(10) = -3.483, p = 0.006), but not in HCs (p > 0.05). Dose-by-time interactions revealed brain temperature increases in the right insula after 0.4 ng/kg (t(12) = -4.074, p = 0.002), but not after 0.3 ng/kg (p > 0.05). Dose-by-time interactions revealed decreased CHO in the right Rolandic operculum after 0.4 ng/kg endotoxin (t(13) = 3.242, p = 0.006) but not 0.3 ng/kg. In the left paracentral lobule, CHO decreased after 0.3 ng/kg (t(9) = 2.574, p = 0.030) but not 0.4 ng/kg. Dose-by-time interactions affected MI in several brain regions. MI increased after 0.3 ng/kg in the right Rolandic operculum (t(10) = -2.374, p = 0.039), left supplementary motor area (t(9) = -2.303, p = 0.047), and left occipital lobe (t(10) = -3.757, p = 0.004), with no changes after 0.4 ng/kg (p > 0.05). Group-by time interactions revealed decreased NAA in the left Rolandic operculum in FM (t(13) = 2.664, p = 0.019), but not in HCs (p > 0.05). A dose-by-time interaction showed decreased NAA in the left paracentral lobule after 0.3 ng/kg (t(9) = 3.071, p = 0.013) but not after 0.4 ng/kg (p > 0.05). In the combined sample, there was a main effect of time whereby NAA decreased in the left anterior cingulate (F[1,21] = 4.458, p = 0.047) and right parietal lobe (F[1,21] = 5.457, p = 0.029). ConclusionWe found temperature increases and NAA decreases in FM that were not seen in HCs, suggesting that FM patients may have abnormal immune responses in the brain. The 0.3 and 0.4 ng/kg had differential effects on brain temperature and metabolites, with neither dose effecting a stronger response overall. There is insufficient evidence provided by the study to determine whether FM involves abnormal central responses to low-level immune challenges.

Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, although their contribution to the painful symptoms remains unknown. Our previous study reported the ability of splenocytes to develop pain-like behavior and an association between the central nervous system (CNS) and splenocytes. Since the spleen is directly innervated by sympathetic nerves, this study aimed to examine whether adrenergic receptors are necessary for pain development or maintenance using an acid saline-induced generalized pain (AcGP) model (an experimental model of fibromyalgia) and whether the activation of these receptors is also essential for pain reproduction by the adoptive transfer of AcGP splenocytes. The administration of selective β2-blockers, including one with only peripheral action, prevented the development but did not reverse the maintenance of pain-like behavior in acid saline-treated C57BL/6J mice. Neither a selective α1-blocker nor an anticholinergic drug affects the development of pain-like behavior. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that peripheral β2-adrenergic receptors play an important role in the efferent pathway from the CNS to splenocytes in pain development.

Fibromyalgia Pathophysiology.

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.

Oxidative Stress in Fibromyalgia: From Pathology to Treatment.

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain associated with sleep problems, fatigue, depression, and anxiety. The persistence of pain, impairment of cognitive function, and negative impact on the psychological state have caused a detrimental effect on the patients' quality of life. However, to date, the treatment and mechanisms of this disease are yet to be established. Oxidative stress might play a critical role in FM pathophysiology. Increased levels of prooxidative factors such as nitric oxide, lipid peroxidation, and mitophagy can cause pain sensitization in fibromyalgia. Numerous studies have supported the hypothesis of beneficial antioxidative effects in FM. Due to the lack of effective therapy for fibromyalgia, many treatments are sought to reduce pain and fatigue and improve patients' quality of life. This manuscript discusses the impact of various antioxidative procedures that can diminish fibromyalgia symptoms, such as hyperbaric oxygen therapy, modification of dietary habits, and physical activity.

Sound-Induced Flash Illusions Support Cortex Hyperexcitability in Fibromyalgia.

Objectives Fibromyalgia (FM) is characterized by spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli. Sound-induced flash illusions (SIFIs) reflect cross-modal interactions between senses allowing to assess a visual cortical hoerexcitability (VCH) by evaluating the fission and fusion illusions disruption. The aims of the present study were to explore whether SIFIs are perceived differently in patients with fibromyalgia as compared to healthy controls (HCs) and how migraine affects fission and fusion illusions in fibromyalgia. Methods A single flash (F) accompanied by 0 to 4 beeps (B) was presented to induce the fission illusion while multiple flash (i.e., 2 to 4) accompanied by 0 or 1 beep was presented to induce fusion illusion. The mean number of perceived flashes in fission and fusion illusion trials was compared between the groups (i.e., FM, FM with migraine, and HCs) using repeated-measures analysis of variance. Medication history was recorded along with the administration of Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression scales. Results Twenty-four patients with FM (mean age 51, 2 ± 10, 6 years; 22 females), seventeen patients with FM and migraine without aura (mean age 47.8 ± 11.4 years; 16 females; 13 chronic, 4 episodic migraine), and forty-one age- and sex-matched HCs (mean age 47.3 ± 6.9 years; 34 females) participated in the study. Fission and fusion illusory effects were detected in all the participants. However, in FM patients, the fission illusion was reduced and almost abolished as compared to HCs (1F1B, p = 0.02; 1F2B, p < 0.0001; 1F3B, p < 0.0001; 1F4B, p = 0.0001), while there were no differences between groups in fusion trials. Migraine did not affect the fission and the fusion illusions. Conclusion Results from this study confirm that patients with FM have a VCH suggesting that the pathological changes in cortical excitability might have important roles in the pathophysiology of FM. SIFI represents a noninvasive behavioral tool for the exploration of cross-sensory functional interplay.

Relationships of autonomic dysfunction with disease severity and neuropathic pain features in fibromyalgia: is it really a sympathetically maintained neuropathic pain?

BackgroundThe pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP.MethodsTwenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire.ResultsFM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although non-significant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities.ConclusionsANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.

Omics approaches to discover pathophysiological pathways contributing to human pain.

Omics approaches to discover pathophysiological pathways contributing to human pain.

Serum anti-neural immunoreactivity in patients with fibromyalgia. Preliminary study.

Fibromyalgia (FM) is a non-degenerative syndrome characterized by generalized, chronic musculoskeletal pain, as well as mood, memory and sleep disorders. To search for serum anti-neural antibodies (ANeuA) in patients with FM (FMP) in order to rule out autoimmune etiology. The Fibromyalgia Impact Questionnaire (FIQ) and Beck's depression inventory (BDI) were applied. Immunoreactivity and the target recognized on the sera from FMPs and healthy subjects were analyzed by indirect immunofluorescence and Western blot. Both FIQ and BDI values were significantly altered in FMPs in comparison with those of controls (FIQ, 70 ± 25 vs. 12 ± 12, p < 0.0001; BDI, 17 ± 11 vs. 4 ± 3, p < 0.0002). Only five out of 15 FMP sera had ANeuA specifically directed against neurons from the medial vestibular nucleus of the brainstem. This immunoreactivity was not detected in the sera from the 14 controls. ANeuA recognized a 45 kDa protein. 30% of FMPs have ANeuA that have not been described before. In future studies, it will be necessary for anti-neural immunoreactivity to be determined in a larger sample and for the role of ANeuAs in the pathophysiology of FM to be established.

Inflammation and Interferon Signatures in Peripheral B-Lymphocytes and Sera of Individuals With Fibromyalgia.

Fibromyalgia (FM) is an idiopathic chronic disease characterized by widespread musculoskeletal pain, hyperalgesia and allodynia, often accompanied by fatigue, cognitive dysfunction and other symptoms. Autoimmunity and neuroinflammatory mechanisms have been suggested to play important roles in the pathophysiology of FM supported by recently identified interferon signatures in affected individuals. However, the contribution of different components in the immune system, such as the B-lymphocytes, in the progression to FM are yet unknown. Furthermore, there is a great need for biomarkers that may improve diagnostics of FM. Herein, we investigated the gene expression profile in peripheral B-cells, as well as a panel of inflammatory serum proteins, in 30 FM patients and 23 healthy matched control individuals. RNA sequence analysis revealed 60 differentially expressed genes when comparing the two groups. The group of FM patients showed increased expression of twenty-five interferon-regulated genes, such as S100A8 and S100A9, VCAM, CD163, SERPINA1, ANXA1, and an increased interferon score. Furthermore, FM was associated with elevated levels of 19 inflammatory serum proteins, such as IL8, AXIN1, SIRT2 and STAMBP, that correlated with the FM severity score. Together, the results shows that FM is associated with an interferon signature in B-cells and increased levels of a set of inflammatory serum proteins. Our findings bring further support for immune activation in the pathogenesis of FM and highlight candidate biomarkers for diagnosis and intervention in the management of FM.

Variable Voxel-based Morphometry Observations of Gray Matter Differences in Fibromyalgia: Individual Differences or Methodological Inconsistency?

Fibromyalgia is a prevalent chronic pain condition characterized by widespread pain and sensory hypersensitivity. While much remains to be learned about the neurobiological underpinnings of this condition, alterations to the central nervous system appear to be heavily implicated in fibromyalgia's pathophysiology. Previous research examining brain structural abnormalities among fibromyalgia patients has yielded inconsistent findings. Thus, we followed previous voxel-based morphometry methods in magnetic resonance imaging to examine brain gray matter differences in females (n=17) with fibromyalgia and female healthy controls (n=17). We hypothesized that, relative to healthy control participants, fibromyalgia participants would exhibit lower gray matter volume in regions consistently implicated in pain processing and, specifically, fibromyalgia: the anterior cingulate cortex and the medial prefrontal cortex. Previously reported peak coordinates are located in both the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC), but interpretation of these locations is varied. Therefore, we first examined a large region of interest that encompassed both the mPFC and ACC, followed by a whole brain analysis. Group differences were analyzed with two-sample t-tests, controlling for total intracranial volume. No significant differences in regional or whole brain gray matter volumes were detected between fibromyalgia patients and healthy controls. These results add to an existing body of disparate findings regarding brain gray matter volume differences in fibromyalgia, and suggest structural differences previously detected among fibromyalgia patients should be rigorously examined for reproducibility and support the need for additional meta-analyses. Absent significant differences may also suggest that individual differences, rather than methodological variability, account for contradictory results. Grant support from K99DA040154.

Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives.

Fibromyalgia (FM) is a prevalent, chronic condition without a cure or reliable therapy. The etiopathogenesis of this syndrome is ambiguous, which has heightened the challenge of discovering treatments to minimize patients’ painful symptoms. FM is characterized by diffuse musculoskeletal pain usually accompanied by functional pain syndromes, such as fatigue, sleep disturbances, cognitive difficulties, and mood issues. Currently available treatment options for FM are limited. Recent studies have suggested a potential role for dietary bioactive compounds in FM management. We performed a narrative review to evaluate the existing evidence regarding the dietary bioactive compounds for FM, and we proposed molecular mechanisms on this topic. The inclusion criteria were (i) human, in vivo, or in vitro studies, (ii) studies related to the effect of bioactive compounds on FM-like symptoms, (iii) peer-reviewed literature, and (iv) publications until February 2022 in PubMed and Google Scholar. Exclusion criteria were (i) study designs using CCI, SNI, or SNL models because they are more NP models rather than FM models, and (ii) studies published in a language other than English. Keywords were dietary bioactive compounds, fibromyalgia, cell, animals, humans. Here, we report the effects of commonly consumed bioactive compounds (capsaicin, ginger, curcumin, n-3 PUFA, grape seed extract, naringin, and genistein) on FM-like symptoms in cellular, animal, and human studies. Cellular studies demonstrated that these bioactive compounds reduce pro-inflammatory production and increase antioxidant capacity of neurons or myoblasts that regulate apoptosis/cell survival. Animal studies showed that these regularly consumed bioactive compounds have an effect on FM-like symptoms, as evidenced by decreased pain hypersensitivity and fatigue as well as improved social behaviors. Further studies are warranted to allow meaningful comparison and quantification of the efficacy of these bioactive compounds on FM-like symptoms across studies, in terms of actual changes in antioxidant capacity, pain hypersensitivity, fatigue, and social behaviors. To date, human studies regarding the efficacy of these bioactive compounds on FM-like symptoms are limited and inconclusive. Our review identifies this important knowledge gap and proposes that the development and use of improved preclinical FM models are needed, particularly concerning the usage of female animals to better mimic FM pathophysiology and symptomatology.

Zinc in fibromyalgia patients: relationship with body mass index and sleep quality

Introduction and aim. Given the potential relationship between oxidative stress and fibromyalgia and well-documented antioxidant efficacy of zinc, the present study aimed to determine serum zinc concentration in FM patients as compared to healthy controls, as well as to identify the correlation of serum zinc concentration with the body mass index (BMI) and sleep quality, Material and methods. In this case-control study, 54 fibromyalgia patients were consecutively recruited between October 01, 2021 and December 01, 2021. The control group consisted of 54 age- and sex-matched healthy controls. Results. Fibromyalgia group had significantly lower zinc concentration, higher body mass index, and lower sleep quality scores as compared to the healthy control group. The correlation analysis revealed a significantly negative correlation between serum zinc concentration and body mass index and a significantly positive correlation between serum zinc concentration and sleep quality both in fibromyalgia and healthy control groups. Conclusion. Our results both support the hypothesis that low serum zinc concentration plays a role in the pathophysiology of fibromyalgia and indicate that fibromyalgia may lead to weight gain and poor sleep quality, which needs to be confirmed in large-cohort studies.