Understanding spinal gout: A comprehensive study of 88 cases and their clinical implications.

Background: Spinal gout, a rare and often underdiagnosed condition, significantly impacts patients' quality of life. Therefore, the aim of the research is to analyze cases of spinal gout, including clinical features, anatomical location of spinal gout, laboratory studies, imaging studies, treatment choices, and outcomes from various cases of spinal gout. Methods: The author conducted a systematic literature search in the PUBMED and Science Direct databases from 2013 to 2023. We included clinical case presentations of spinal cases in adults, published in English. The three researchers independently reviewed the title and abstract of each article, and any differences in opinions were resolved through consensus. The extracted data were subsequently analyzed descriptively. Results: A total of 88 cases of spinal gout were obtained and studied. Out of the total reviewed cases of spinal gout, 89.77% of the subjects were male, with an average age of 51.9 years (age range 16-87 years). Common symptoms include back/neck pain (78.41%) and lower extremity weakness (37.50%). The lumbar spine is the most frequently affected region (62.50%), diagnosed primarily through magnetic resonance imaging (MRI) scans. Surgery, performed in 61.36% of cases, commonly involves decompressive laminectomy. Posttreatment, symptoms resolve in 87.50% of cases. Conclusion: Cases of spinal gout present with a variety of symptoms, including back pain and weakness. Diagnosis typically involves an MRI examination and synovial fluid analysis for confirmation. Treatment varies and includes medication therapy and surgical interventions. A deeper understanding of these cases can assist healthcare practitioners in the management and diagnosis of spinal gout cases.

Elucidating the mechanism of the Tibetan medicine sanguotang in treating gouty arthritis through network pharmacology and in vivo experiments.

BACKGROUND: We explored the mechanisms of Sanguotang (SGT), a Tibetan medicine, in treating gout arthritis (GA). METHODS: The main active components, action targets, and disease targets of SGT were identified through TCMSP databases. The gene functions were analyzed using protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking. A GA model induced by monosodium urate was established in rats. The ankle joint swelling was observed. The levels of uric acid (UA) and albumin (ALB) in rat serum were measured. Hematoxylin and eosin (HE) staining was conducted to examine the pathological changes in rat ankle joints. RESULTS: Twenty-nine active components of SGT with proven efficacy and 66 intersection targets were identified, primarily involved in inflammation and immune regulation pathways. The PPI results revealed that the key targets of SGT against GA included ALB, IL6, TNF, TP53, and PTGS. Molecular docking showed favorable binding energy between the ALB protein and the active components. The results from animal experiments demonstrated that SGT effectively alleviated the inflammatory reaction in ankle joints, and decreased UA and ALB levels. Furthermore, SGT effectively inhibited the proliferation of synovial cells in the ankle joint cavity, prevented infiltration of inflammatory cells, and protected synovial tissue, thereby improving GA. CONCLUSIONS: SGT comprehensively contributes to the treatment of GA by regulating UA metabolism, reducing the release of inflammatory factors, and modulating immune and inflammatory pathways.

Bioactive Phosphorus Dendrimers as a Universal Protein Delivery System for Enhanced Anti-inflammation Therapy.

Nanocarrier-based cytoplasmic protein delivery offers opportunities to develop protein therapeutics; however, many delivery systems are positively charged, causing severe toxic effects. For enhanced therapeutics, it is also of great importance to design nanocarriers with intrinsic bioactivity that can be integrated with protein drugs due to the limited bioactivity of proteins alone for disease treatment. We report here a protein delivery system based on anionic phosphite-terminated phosphorus dendrimers with intrinsic anti-inflammatory activity. A phosphorus dendrimer termed AK-137 with optimized anti-inflammatory activity was selected to complex proteins through various physical interactions. Model proteins such as bovine serum albumin, ribonuclease A, ovalbumin, and fibronectin (FN) can be transfected into cells to exert their respective functions, including cancer cell apoptosis, dendritic cell maturation, or macrophage immunomodulation. Particularly, the constructed AK-137@FN nanocomplexes display powerful therapeutic effects in acute lung injury and acute gout arthritis models by integrating the anti-inflammatory activity of both the carrier and protein. The developed anionic phosphite-terminated phosphorus dendrimers may be employed as a universal carrier for protein delivery and particularly utilized to deliver proteins and fight different inflammatory diseases with enhanced therapeutic efficacy.

The role of acid-sensing ion channels in monosodium urate-induced gouty pain in mice.

Acid-sensing ion channels (ASICs) in dorsal root ganglion (DRG) neurons play an important role in inflammatory pain. The objective of this study is to observe the regulatory role of ASICs in monosodium urate (MSU) crystal-induced gout pain and explore the basis for ASICs in DRG neurons as a target for gout pain treatment. The gout arthritis model was induced by injecting MSU crystals into the ankle joint of mice. The circumference of the ankle joint was used to evaluate the degree of swelling; the von Frey filaments were used to determine the withdrawal threshold of the paw. ASIC currents and action potentials (APs) were recorded by patch clamp technique in DRG neurons. The results displayed that injecting MSU crystals caused ankle edema and mechanical hyperalgesia of the paw, which was relieved after amiloride treatment. The ASIC currents in DRG neurons were increased to a peak on the second day after injecting MSU crystals, which were decreased after amiloride treatment. MSU treatment increased the current density of ASICs in different diameter DRG cells. MSU treatment does not change the characteristics of AP. The results suggest that ASICs in DRG neurons participate in MSU crystal-induced gout pain.

Mechanistic prospective and pharmacological attributes of quercetin in attenuation of different types of arthritis.

Arthritis is a frequent autoimmune disease with undefined etiology and pathogenesis. Scientific community constantly fascinating quercetin (QUR), as it is the best-known flavonoid among others for curative and preventive properties against a wide range of diseases. Due to its multifaceted activities, the implementation of QUR against various types of arthritis namely, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis (GA) and psoriotic arthritis (PsA) has greatly increased in recent years. Many research evidenced that QUR regulates a wide range of pathways for instance NF-κB, MAK, Wnt/ß-catenine, Notch, etc., that are majorly associated with the inflammatory mechanisms. Besides, the bioavailability of QUR is a major constrain to its therapeutic potential, and drug delivery techniques have experienced significant development to overcome the problem of its limited application. Hence, this review compiled the cutting-edge experiments on versatile effects of QUR on inflammatory diseases like RA, OA, GA and PsA, sources and bioavailability, therapeutic challenges, pharmacokinetics, clinical studies as well as toxicological impacts. The use of QUR in a health context would offer a tearing and potential therapeutic method, supporting the advancement of public health, particularly, of arthritic patients worldwide.

Manganese-doped albumin-gelatin composite nanogel loaded with berberine applied to the treatment of gouty arthritis in rats via a SPARC-dependent mechanism.

In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.

The inflammation process of gout arthritis and its treatment.

Gout arthritis is an inflammatory condition that occurs suddenly in joints affected by high uric acid levels (hyperuricemia). The uric acid levels in this disease fluctuate throughout its various phases, resulting in frequent or recurrent attacks. This study aims to review some aspects of gout arthritis, such as its pathophysiology, treatment goals, and adverse drug reactions. This study employs review literature using articles published between 2017 and 2022 as the research methodology. Furthermore, articles under 2017 are used as references if they are relevant to the study's subject matter. The findings showed the importance of the pathogenesis of inflammation in the treatment of gout arthritis. It is also recommended to use anti-inflammatories such as colchicine and uric acid-lowering medications starting at a specific time to prevent unintended risks. Hence, pharmacotherapy management's adverse effects include nausea, vomiting, myalgia, neuropathy, and stomach pain.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

OBJECTIVES: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. METHODS: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. RESULTS: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). CONCLUSIONS: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Gut microbiota mediated the therapeutic efficiency of Simiao decoction in the treatment of gout arthritis mice.

BACKGROUND: Gut microbiota plays a significant role in the development and treatment of gouty arthritis. Simiao decoction has been shown to alleviate gouty arthritis by inhibiting inflammation, regulating NLRP3 inflammasome, and altering gut microbiota. However, there is no evidence to prove whether gut microbiota directly mediates the therapeutic efficiency of Simiao decoction in treating gout arthritis. METHODS: In this study, fecal microbiota transplantation (FMT) was used to transfer the gut microbiota of gout arthritis mice treated with Simiao decoction or allopurinol to blank gout arthritis mice, in order to investigate whether FMT had therapeutic effects on gout arthritis. RESULTS: Both Simiao decoction and allopurinol effectively reduced the levels of serum uric acid, liver XOD activity, foot thickness, serum IL-1ß, and G-CSF in gout arthritis mice. However, Simiao decoction also had additional benefits, including raising the pain threshold, reducing serum TNF-α and IL-6, alleviating gut inflammation, and repairing intestinal pathology, which were not observed with allopurinol treatment. Moreover, Simiao decoction had a greater impact on gut microbiota than allopurinol, as it was able to restore the abundance of phylum Proteobacteria and genus Helicobacter. After transplantation into gout arthritis mice, gut microbiota altered by Simiao decoction exhibited similar therapeutic effects to those of Simiao decoction, but gut microbiota altered by allopurinol showed no therapeutic effect. CONCLUSIONS: These findings demonstrates that Simiao decoction can alleviate gout arthritis symptoms by regulating gut microbiota.

Role of NLRP3 in the pathogenesis and treatment of gout arthritis.

Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1ß, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1ß, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.

A retrospective observational study of the appropriate starting dose of febuxostat in patients with gout.

BACKGROUND/AIMS: The occurrence of gout attacks at the start of uric acid lowering treatment worsens compliance. We aimed to determine the appropriate dose of febuxostat to reduce the occurrence of gout attacks during the initial treatment period. METHODS: We retrospectively analyzed the data of patients diagnosed with gout who underwent treatment at Jeju National University Hospital between May 2018 and May 2020. RESULTS: Two-hundred and twenty-seven patients were included, with a mean age of 53.2 ± 16.4 years, and 219 (96.5%) were male. The patients were divided into two groups according to the starting dose of febuxostat (20 mg vs. 40 mg). There were no significant differences in mean age, disease duration, colchicine, estimated glomerular filtration rate (eGFR), initial uric acid levels, and presence of subcutaneous tophi between the two groups. Gout attacks occurred more frequently in the 20 mg group than in the 40 mg group during the first 3 months of treatment (32.0% vs. 14.3%, p = 0.002), particularly during the first month (21.3% vs. 7.5%, p = 0.005). Multivariate logistic regression analysis was conducted adjusting for the effects of disease duration, the presence of subcutaneous tophi, eGFR, and initial uric acid levels. A febuxostat starting dose of 40 mg (odds ratio, 0.464; 95% confidence interval [CI], 0.246 to 0.862; p = 0.015) and anti-inflammatory prophylaxis (odds ratio, 0.359; 95% CI, 0.158 to 0.813; p = 0.014) were found to be independent factors associated with a gout attack. CONCLUSION: Starting uric acid lowering treatment with febuxostat 40 mg rather than 20 mg may reduce the incidence of gout attacks in the early period of treatment in Korean patients with gout.

Role of NINJ1 in Gout Flare and Potential as a Drug Target.

Objective: To determine the role of nerve injury-induced protein 1 (NINJ1) introduced plasma membrane rupture (PMR) and damage-associated molecular patterns (DAMPs) release in the pathogenesis and progression of gout and to explore the potential of NINJ1 as a therapeutic target in gout. Methods: Both peripheral blood mononuclear cells (PBMCs) and serum sample from gout patients (n = 58) and healthy controls (n = 16) were collected and processed to NINJ1 expression, lactate dehydrogenase (LDH) detection, NINJ1 inhibition, and NINJ1 expression experiments, respectively. NINJ1 knockdown was carried out by lentivirus in a monosodium urate (MSU) induced rat model, and NINJ1 neutralizing antibody was applied in a MSU induced mouse model. Results: Our results found that NINJ1 was upregulated during a gout flare, and the resulting induction of PMR correlated with gout progression. NINJ1 knockdown significantly reduced the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and joint swelling in the rat model, and NINJ1 neutralizing antibody also significantly reduced gout flare in the mouse model and PBMCs. Moreover, NINJ1 expression is under NLRP3 inflammasome produced interleukin (IL)-1ß control. Conclusion: These results support the notion of a pathogenic role of NINJ1 introduced PMR in gout and provide a detailed mechanism for gout pathogenesis involving inflammatory cell death and DAMPs release introduced by IL-1ß. In addition, targeting NINJ1 might be a potential therapeutic approach for gout.

Study on the effect and mechanism of quercetin in treating gout arthritis.

Quercetin is widely found in natural plants, especially Chinese herbal plants. It has been used to treat arthritis in China for thousands of years. However, the effects and mechanisms of quercetin in the treatment of gout arthritis (GA) remain unclear. We aimed to verify the treatment of GA with quercetin and investigate the underlying mechanism. A combination of network pharmacology and experiments was used to reveal the mechanism of quercetin in the treatment of GA. Potential targets of quercetin and gout were identified. Then, the protein-protein interaction network for the common targets between quercetin and gout was constructed and the core targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the common targets were performed to elucidate the pharmacological functions and mechanisms associated with quercetin treatment in GA. Finally, a monosodium urate-induced GA rat model was used to validate the predicted mechanisms in network pharmacology. Seventy-two common targets were identified. KEGG analysis revealed that treatment of GA with quercetin predominantly involved the interleukin (IL)-17, tumor necrosis factor (TNF), mitogen-activated protein kinase, and phosphoinositide 3-kinase-Akt signaling pathways. In an experimental validation, quercetin attenuated ankle joint inflammation-induced bone destruction and histological lesions. It also diminished the expression of IL-6, IL-17A, and IL-17F in the IL-17 pathway, and regulated the release of RAR-related orphan receptor gamma t,IL-17E, IL-1ß, IL-6, TNF-α, Foxp3, and transforming growth factor-beta 1. The collective findings implicate quercetin as a valuable alternative drug for the treatment of GA.

Urate-lowering therapy for patients with gout on hemodialysis.

OBJECTIVE: Gout is the most common form of inflammatory arthritis and is caused by deposition of monosodium urate crystals resulting from a high burden of uric acid (UA). High UA burden also has been associated with increased morbidity and mortality in the general population and progression to chronic kidney disease. In persons with gout and end-stage renal disease (ESRD), prior studies suggest that UA levels decrease after initiation of hemodialysis (HD). We evaluated UA level and the use of urate-lowering therapies (ULTs) in patients with gout and ESRD on HD. METHODS: We performed a retrospective review of patients with gout and ESRD seen at a large urban public hospital (The MetroHealth System). We extracted data from the medical record (Epic) for patients diagnosed with gout and ESRD on HD. The main outcomes were the UA level and the use of ULTs before and after HD initiation. RESULTS: We identified 131 patients with gout on HD. Of these, 21 patients had crystal proven gout diagnosis, 10 of whom had data on UA level pre-HD and post-HD and were included in the analysis. For the total sample (N = 21), the mean age was 65 years, 7 were female and 20 were African American. Mean pre-HD and post-HD UA levels were 8.4 and 3.98 mg/dL respectively. Twenty-one patients were receiving ULT pre-HD, 11 discontinued post-HD. CONCLUSION: Among patients with gout and ESRD, we observed a decrease in UA level associated with initiation of HD. For this group, discontinuation of ULTs may be appropriate.

The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis.

Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aß. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 µM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.

COVID-19 in patients with gout on colchicine.

Current data demonstrated that severe cases of coronavirus-disease-19 (COVID-19) require treatment with antiviral therapy, dexamethasone, supportive care, as well as some anti-rheumatic drugs, among them, cytokine inhibitors and colchicine. Colchicine is an anti-inflammatory drug that is being used in rheumatology for many years to treat mostly gout, calcium pyrophosphate deposition disease, and Familial Mediterranean Fever. Here, we present for the first time, two patients suffering from gout being treated with colchicine, who were affected from severe acute respiratory coronavirus-2 (SARS-CoV-2) syndrome. Both patients presented with mild symptoms of COVID-19 expressed with myalgias, arthralgias, and sore throat, while laboratory investigations showed only high acute phase reactants. Four weeks later, both patients were free of symptoms with negative SARS-CoV-2 tests and without any complications. To our knowledge, there are no other studies of gout arthritis and SARS-CoV-2 infection published so far. Thus, our preliminary conclusion is that chronic use of colchicine may mitigate the clinical picture and disease course of COVID-19 in gout arthritis patients. Further studies with a large number of patients are needed to confirm the above beneficial effect of colchicine.

MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3.

Down-regulated miR-223-3p was found in rheumatoid arthritis. This study aimed to further explore the level and role of miR-223-3p in gout arthritis (GA). After monosodium urate (MSU)-induced GA rat and fibroblast-like synoviocytes (FLSs) models were established, the rat paw volume and gait score were documented and the FLSs were transfected with miR-223-3p mimic/inhibitor or NLR family pyrin domain containing 3 (NLRP3) over-expression plasmids. The MiR-223-3p target was found through bioinformatics and the dual-luciferase reporter. The rat joint pathological damage was observed by hematoxylin and eosin staining. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and articular elastase in rats were detected by enzyme-linked immunosorbent assay (ELISA). The viability and pyroptosis of FLSs were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry. The expressions of miR-223-3p, NLRP3, cleaved caspase-1, IL-1ß, apoptosis-associated speck-like protein (AS) and cleaved N-terminal gasdermin D (GSDMD) in FLSs or rat synovial tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Western blot or immunohistochemistry analysis. MSU increased the paw volume, gait score, inflammation in synovial tissues and increased the levels of IL-1ß, TNF-α and articular elastase in rats. MSU decreased the viability and increased the pyroptosis of FLSs, up-regulated the expression of NLRP3, ASC, cleaved caspase-1, cleaved N-terminal GSDM, and IL-1ß, and down-regulated miR-223-3p expression in synovial tissues of rat joints and FLSs. MiR-223-3p mimic reversed the effect of MSU on lowering cell viability, increasing pyroptosis in FLSs, while miR-223-3p inhibitor further enhanced the effect of MSU on FLSs. NLRP3 was a target of miR-223-3p. Also, NLRP3 over-expression reversed the effects of miR-223-3p on MSU-induced FLSs. MiR-223-3p inhibited pyroptosis in MSU-induced rats and FLSs by targeting NLRP3.

Antinociceptive Efficacy of Retigabine and Flupirtine for Gout Arthritis Pain.

INTRODUCTION: Gout arthritis is an inflammatory disease characterized by severe acute pain. The goal of pharmacological gout arthritis treatments is to reduce pain, and thereby increase the patient's quality of life. The Kv7/M channel activators retigabine and flupirtine show analgesic efficacy in animal models of osteoarthritic pain. We hypothesized that these drugs may also alleviate gout arthritis pain. OBJECTIVE: To determine the effects of retigabine and flupirtine on pain behavior associated with monosodium urate (MSU)-induced gout arthritis. METHODS: The gout arthritis model was established with an intra-articular injection of MSU into the right ankle joint, animals were treated with retigabine or flupirtine, and pain-related behaviors were assessed. RESULTS: Retigabine and flupirtine significantly increased the mechanical threshold and prolonged the paw withdrawal latency in a rat model of gout arthritis pain in a dose-dependent manner. The antinociceptive effects of retigabine and flupirtine were fully antagonized by the Kv7/M channel blocker XE991. CONCLUSION: Retigabine and flupirtine showed antinociceptive effects for MSU-induced gout pain at different times during pain development.

Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis using network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Porana sinensis Hemsl. has been widely used to treat joint pain and rheumatoid arthritis in traditional Chinese medicine (TCM). Although evidence exists to support a pharmacological action of P. sinensis for the treatment of gout arthritis (GA), the underlying mechanism of action remains unknown due to it being a multi-component and multi-target agent. AIM OF THE STUDY: To clarify the active compounds and mechanism of P. sinensis against GA. MATERIALS AND METHODS: The present study combined network pharmacology with experiments to clarify the mechanism of P. sinensis against GA. A protein-protein interaction network for gout was constructed to identify the potential drug targets, and molecular docking was subsequently performed to determine whether the protein was a target for the compounds of P. sinensis. KEGG pathway analysis was then conducted to elucidate the pathway involved in the P. sinensis-mediated treatment of gout. A rat model of GA was used to further investigate the mechanism of P. sinensis against GA. RESULTS: The network pharmacology study indicates that coumarins and chlorogenic acids of P. sinensis may serve as additives to GA treatment. P. sinensis played a role in the treatment of GA by regulating the PI3K-Akt, MAPK, NF-kappa B and toll-like receptor pathways and so on. Moreover, experimental validation suggests that P. sinensis extract significantly suppressed the expression of TLR2 and MyD88 mRNA, regulating the release of cytokines (IL-1ß, IL-4 and TGF-ß), lowering lipid peroxidation (MDA) and increasing antioxidant status (SOD). CONCLUSION: The present study clarifies the mechanism of P. sinensis against GA, and provides evidence to support its clinical use.

Pathological Fracture of the Femoral Neck due to Tophaceous Gout: An Unusual Case of Gout.

A 48-year-old man visited the emergency room with right hip pain that started abruptly while walking out of the bathroom. Computed tomography showed an intraosseous mass in the femoral neck. The patient had a 15-year history of gout and had numerous bilateral tophi in his hands, feet, knees, and elbows. After operation, we diagnosed a pathological fracture due to intraosseous tophi. Patients with hip pain who have many subcutaneous tophi and long-standing gout should be diagnosed carefully. Peri-hip joint pain caused by gout is uncommon, however, if a patient complains of pain, a simple X-ray may be required. If intraosseous tophi are present, appropriate treatment (e.g., strict hyperuricemia control with or without prophylactic internal fixation), may be required before fracture occurs.