Search Results (404)

Background: Fibromyalgia syndrome (FMS) is a complex condition with poorly understood pathophysiology, characterized by widespread pain and an increasing recognition of its associations with genitourinary symptoms. The objective of this study was to characterize the prevalence, phenotype, and common comorbidities of lower urinary tract symptoms (LUTS) in women with FMS. Methods: A retrospective observational study was conducted using electronic medical records of 440 women diagnosed with FMS at a single institution between 1 January 2018, and 1 January 2024. Study subjects were evaluated for diagnoses associated with LUTS, including interstitial cystitis (IC), overactive bladder (OAB), and stress urinary incontinence (SUI), alongside comorbidities such as irritable bowel syndrome (IBS), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Multivariate analyses were performed to assess predictors of conditions associated with LUTS. Results: LUTS were identified in 37.0% of FM patients. GAD and IBS were significantly associated with conditions associated with LUTS (OR = 4.62; OR = 8.53, p < 0.001). SUI was present in 17.05% of patients, falling between survey-based and confirmed prevalence rates in the general population. IC was diagnosed in 2.95% of FMS patients. OAB was observed in 6.8% of patients and associated with GAD (OR = 5.98, p < 0.001). Conclusions: This study highlights a substantial burden of diagnoses associated with LUTS in patients with FMS. There is relatively high prevalence of SUI and IC in this dataset. IBS and GAD were commonly found to co-occur with one or more LUTS-associated condition. Future prospective studies are needed to investigate a multimodal approach to the treatment of LUTS in these patients. Full article

Background: Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, cognitive difficulties, and psychological symptoms. Patients often present distinct personality traits and psychopathological patterns associated with symptom severity. Objective: To examine psychopathological profiles in FM patients based on functional, physical–somatic, and emotional impairment domains, as well as on cumulative disease severity. Materials and Methods: A cross-sectional study was conducted with 70 women clinically diagnosed with FM at a specialized Fibromyalgia Unit. Psychological functioning was assessed using the Personality Assessment Inventory, and disease impact was measured with the Fibromyalgia Impact Questionnaire. Hierarchical cluster analyses were used to classify participants into mild and severe clusters across FIQ domains, and psychological profiles were compared. Results: Patients with severe functional impairment had more affective dysregulation (76.43 vs. 70.20, p < 0.01) and somatic complaints (85.57 vs. 79.76, p < 0.05) than those with mild impairment. The severe–physical cluster showed greater mood instability, somatization, and suicidal ideation (60.94 vs. 53.61, p < 0.05). The severe–emotional cluster had higher rates of major depression (85.71% vs. 64.28%) and persistent depressive disorder (76.19% vs. 70.61%, p < 0.05). Severe showed more emotional instability and somatization, distinguishing it from mild. Greater cumulative severity intensified depressive and somatic disorders. Discussion: Findings support FM’s biopsychosocial profile, where emotional distress may relate to psychological and physical symptoms, reinforcing the need for personalized, multidisciplinary care and comprehensive assessment. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Fibromyalgia is a complex disorder characterized by chronic widespread pain and a variety of related symptoms. Growing evidence suggests that the central and peripheral nervous systems are involved, with small fiber neuropathy playing a key role in its development. We retrospectively reviewed the medical records of 100 patients diagnosed with primary fibromyalgia. Those showing symptoms indicative of small fiber dysfunction who were treated with L-Acetyl Carnitine (LAC) and Palmitoylethanolamide (PEA) alongside standard care (SOC) were compared to matched controls who received only SOC. To ensure comparable groups, propensity score matching was used. Changes in Fibromyalgia Impact Questionnaire Revised (FIQR) scores over 12 weeks were analyzed using non-parametric tests due to the data’s non-normal distribution. After matching, 86 patients (43 in each group) were included. The group receiving LAC and PEA as add-on therapy experienced a significant median reduction in FIQR scores (−19.0 points, p < 0.001), while the SOC-only group showed no significant change. Comparisons between groups confirmed that the improvement was significantly greater in the LAC+PEA group (p < 0.001). These results suggest that adding LAC and PEA to standard care may provide meaningful symptom relief for fibromyalgia patients with suspected small fiber involvement. This supports the hypothesis that peripheral nervous system dysfunction contributes to the disease burden in this subgroup. However, further prospective controlled studies are needed to confirm these promising findings. Full article

Background: Postoperative pain management after a cesarean section remains a significant challenge, as inadequate control can delay maternal recovery and hinder early bonding and breastfeeding. While multimodal analgesia is the standard approach, non–pharmacological strategies like immediate skin–to–skin contact (SSC) are often underused despite their potential benefits in reducing pain, improving uterine contractions, and increasing maternal satisfaction. Objective: To evaluate the effects of immediate SSC on postoperative pain perception, uterine contraction quality, and maternal satisfaction, and to explore ways to incorporate SSC into routine post–cesarean care to promote recovery and humanized care. Method: A randomized clinical trial was conducted with 80 women undergoing elective cesarean sections, divided into two groups: SSC (40 women) and control (40 women). Postoperative pain was measured using the Visual Analog Scale (VAS) at various intervals, while uterine contraction quality and maternal satisfaction were assessed through clinical observation and a Likert scale, respectively. Results: We found that women in the SSC group experienced significantly lower pain scores (VAS2 and VAS3, p < 0.001), stronger infraumbilical uterine contractions (92.5%, p < 0.001), and higher satisfaction levels (average 9.98 vs. 6.50, p < 0.001). An inverse correlation was observed between pain intensity and satisfaction, indicating that SSC enhances both physiological and psychological recovery. Conclusions: Immediate SSC after cesarean is an effective, humanizing intervention that reduces pain, supports uterine contractions, and boosts maternal satisfaction. These findings advocate for integrating SSC into standard postoperative care, aligning with ethical principles of beneficence and autonomy. Further research with larger samples is necessary to confirm these benefits and facilitate widespread adoption in maternity protocols. Full article

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Pain is a common condition among older adults and a key factor influencing daily functioning. This cross-sectional study examined how pain presence and distribution (no pain, localized pain [LP], and widespread pain [WP]) are related to limitations in Basic and Instrumental Activities of Daily Living (BADLs and IADLs). Data were drawn from the Survey of Health, Aging, and Retirement in Europe (SHARE) Wave 9, including 68,839 participants aged 50 or older. A clear gradient of functional limitation was observed: Individuals with WP reported the highest number of limitations, followed by those with LP, while those with no pain showed minimal impairment. These associations remained significant after adjusting for age, sex, cognitive status, physical health, and psychosocial factors, with adjusted prevalence ratios (aPRs) for WP of 1.77 for BADLs and 1.22 for IADLs (p < 0.001). Notably, depression, perceived loneliness, long-term illness, physical inactivity, and mobility limitations were especially relevant among participants with WP. The findings suggest the clinical value of assessing and implementing interventions not only in the presence but also in the extent of pain to better identify individuals at greater risk of losing independence in daily life. Full article

This article aims to offer a broad perspective on the use of non-invasive brain stimulation (NIBS) techniques in the context of chronic musculoskeletal pain (CMP) conditions. While NIBS has demonstrated promising efficacy in certain chronic pain populations, its application in the management of CMP remains limited. This paper examines the current evidence supporting the use of NIBS for pain relief in CMP, the rationale and proposed mechanisms of action, the importance of patient selection, common methodological limitations in the existing literature, and the potential adverse effects of these techniques. The authors argue that the current evidence is insufficient to support widespread clinical adoption of NIBS for CMP. Advancing the field will require more rigorous study designs, with adequately powered and properly blinded randomized controlled trials. Additionally, future research should address the identification of potential responders to brain stimulation, conduct economic evaluations, and carefully assess the benefit–risk ratio before NIBS can be integrated into routine clinical practice. Full article

Rilpivirine (RPV, R278474) was highlighted in 2005, two years after the death of Dr. Paul Janssen, as the ideal non-nucleoside reverse transcriptase inhibitor (NNRTI) to treat HIV infections. For this purpose, it was subsequently combined with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), darunavir (boosted with ritonavir or cobicistat) or dolutegravir. Its wide-spread use is thanks to its combination with cabotegravir (CAB) in the form of a long-acting intramuscular injection once per month (QM), later twice per month (Q2M), for the treatment of adults, later extended to adolescents and pregnant women, with HIV infections. The long-acting CAB plus RPV should not be administered in patients treated with rifampicin or rifabutin, patients with virological failure or patients with resistance to CAB or RPV, or patients with hepatitis B virus (HBV) infection. Long-acting CAB+RPV may lead to pain at the site of injection which would diminish over time. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

Fibromyalgia syndrome (FMS) is a complex, heterogeneous disorder characterized by chronic widespread pain, fatigue, and cognitive disturbances. The multifactorial nature of FMS, with the involvement of central and peripheral mechanisms, hampers diagnosis and effective treatment. In recent years, positron emission tomography (PET) imaging has emerged as a valuable tool for exploring the neurobiological underpinnings of FMS. Several studies have investigated alterations in glucose metabolism, neurotransmitter systems (including opioid, dopamine, and GABAergic pathways), and neuroinflammation using various PET tracers. These findings have revealed distinct brain metabolic and molecular patterns in FMS patients compared to healthy controls, particularly in pain-related regions such as the thalamus, insula, and anterior cingulate cortex (ACC). Moreover, preliminary data suggest that PET imaging may help identify FMS subgroups with different pathophysiological profiles, potentially allowing for tailored therapeutic approaches. This review summarizes the current evidence on PET applications in FMS and discusses the potential role of molecular imaging in improving patient stratification and predicting treatment response. Full article

Anesthesia is a cornerstone of modern medicine, enabling surgery, pain management, and critical care. Despite its widespread use, the precise molecular mechanisms of anesthetic action remain incompletely understood. Recent advancements in structural biology, including cryo-electron microscopy (Cryo-EM), X-ray crystallography, and computational modeling, have provided high-resolution insights into anesthetic–target interactions. This review examines key molecular targets, including GABA_A receptors, NMDA receptors, two-pore-domain potassium (K2P) channels (e.g., TREK-1), and voltage-gated sodium (Nav) channels. General anesthetics modulate GABA_A and NMDA receptors, affecting inhibitory and excitatory neurotransmission, while local anesthetics primarily block Nav channels, preventing action potential propagation. Structural studies have elucidated anesthetic binding sites and gating mechanisms, providing a foundation for drug optimization. Advances in computational drug design and AI-assisted modeling have accelerated the development of safer, more selective anesthetics, paving the way for precision anesthesia. Future research aims to develop receptor-subtype-specific anesthetics, Nav1.7-selective local anesthetics, and investigate the neural mechanisms of anesthesia-induced unconsciousness and postoperative cognitive dysfunction (POCD). By integrating structural biology, AI-driven drug discovery, and neuroscience, anesthesia research is evolving toward safer, more effective, and personalized strategies, enhancing clinical outcomes and patient safety. Full article

Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are increasingly recognized as complex, multisystem connective tissue disorders characterized by joint hypermobility and instability, chronic pain, autonomic dysfunction, immune dysregulation, and structural fragility. Despite their clinical impact and prevalence, the underlying pathophysiology remains poorly understood, and diagnosis is frequently delayed or missed altogether. Emerging research highlights the fascia as a central player in the pathogenesis of these conditions. This narrative review synthesizes current molecular, histological, and biomechanical findings to propose a fascia-centered framework for understanding hEDS and HSD. Evidence from transcriptomic and imaging studies reveals consistent abnormalities in fascial thickness, interfascial gliding, myofibroblast activation, tendon elongation, and tissue stiffness—findings that mirror the functional impairments reported in clinical populations. We explore fascia as a dynamic tissue network and consider how dysregulation in these processes may contribute to the widespread symptoms seen in hypermobility disorders. By reframing hEDS and HSD as disorders of pathological fascial remodeling, this review offers an integrated model that connects molecular mechanisms with clinical expression. It underscores the urgent need for multidisciplinary research to define diagnostic biomarkers, clarify therapeutic targets, and support the development of more effective, personalized interventions. Full article

Background: Low back pain (LBP) and musculoskeletal disorders are highly prevalent among agricultural workers. However, there is limited epidemiological evidence from rural regions of Ecuador, where working and living conditions may differ substantially from those in other settings. This study aimed to identify predictors of LBP among farmers in rural Ecuador to inform locally relevant prevention strategies. Methods: Participants aged 30 to 60 years (n = 103) were recruited through a traveling health clinic. Participants were assessed with behavioral and sociodemographic self-report questionnaires and anthropometric measurements. Low back pain (LBP) was assessed using the Standardized Nordic Musculoskeletal Questionnaire, which asked about symptoms experienced in the past 12 months. Bivariate (Chi-square and Fisher exact tests) and multivariate (binary logistic regression) analyses were conducted to explore associations between risk factors and LBP in individuals aged 30 to 60 years. Results: LBP was highly prevalent, affecting 78.6% of participants. Behavioral patterns were mixed, with low rates of smoking and moderate alcohol and coffee consumption associated with LBP. A normal body mass index (BMI) was observed in 66% of the sample, and over half reported stable mood and good self-perceived health. In the binary logistic regression analysis, only education level significantly predicted LBP, with secondary education acting as a protective factor. Conclusions: While lower back pain was widespread in the population studied, most risk factors that were analyzed were not significantly associated with its presence. Full article

Fibromyalgia (FM) is characterized by persistent widespread pain that severely impacts quality of life. Immersive virtual reality-based exercise (iVRE) is emerging as a therapeutic modality for chronic pain management. However, research on iVRE in FM patients has primarily focused on perceived pain intensity (PI), with limited exploration of underlying analgesic mechanisms. This study aims to explore the effects of iVRE on PI, considering risk of poor outcomes (RPO) stratification, and on mechanical pain sensitivity (MPS) in FM. A single-arm, uncontrolled, pre-post-test exploratory study was conducted in subjects with FM. The intervention included 2 weekly 15-min iVRE sessions for 6 weeks. PI (numeric rating scale [NRS]) and MPS (pressure pain thresholds [PPTs] at the upper trapezius, lumbar spine, and knee) were assessed at baseline, after the first session (to assess exercise-induced hypoalgesia), and postintervention. RPO was assessed using the Keele STarT MSK Tool. Eleven participants completed the study. No adverse effects were reported. Clinically important reductions were observed in PI (mean difference [MD]: −2.36, 95% CI: [−4.15, −0.58], d = 0.89; p < 0.05) with this effect being associated with baseline RPO. No observable changes were found in PPTs (all 95% CIs included 0, p > 0.05). In this sample, iVRE appears to reduce PI but not PPTs, suggesting the persistence of MPS and limitations in activating endogenous pain inhibitory mechanisms. Further randomized controlled trials with larger samples are needed to corroborate these results. Full article