Gouty Involvement of Foot and Ankle: Beyond Flares

Bernal, J. A.; Campos, Jonatan García; Marco-Lledó, J.; Andrés, Mariano

doi:10.1016/j.reuma.2019.12.003

Cited by 4 publications

(4 citation statements)

References 62 publications

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“…Gouty arthritis can lead to gait impairment that severely restricts mobility of patients' lower limbs and affects daily activities 41 . Our recent studies demonstrate that MSU-induced gouty arthritis model mice display similar gait impairments 14 , 16 , 37 .…”

Section: Resultsmentioning

confidence: 99%

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Yin,

Lyu,

Dong

et al. 2024

Theranostics

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Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca 2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.

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Section: Resultsmentioning

confidence: 99%

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Yin,

Lyu,

Dong

et al. 2024

Theranostics

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show abstract

“…It is known that gout pain triggers gait impairment among patients, which severely restricts mobility of the lower limbs and impacts daily activities [ 31 ]. We explored whether gout arthritis model mice might develop similar gait impairment as gouty patients and if so, whether EA intervention could reverse it.…”

Section: Resultsmentioning

confidence: 99%

Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

et al. 2023

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Background Gout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain. Methods Monosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca2+ imaging and behavioral assays were applied. Results Model mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA’s inhibitory effect on NLRP3 inflammasome and further reversed EA’s anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca2+ imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout. Conclusions Our results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.

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“…Estimando que hasta un 50 % de la población no calza una talla adecuada 23 , y que esta situación se asocia al aumento del dolor y trastornos en los pies 24 , es importante destacar la importancia de recibir unos consejos apropiados sobre el calzado en general y en los pies de pacientes con LES en particular. La importancia del calzado ha sido detallada en otras enfermedades reumáticas como la artritis reumatoide 25 y la gota 26 , entre otras.…”

Section: Discussionunclassified

Dolor, uso de ortesis plantares, calzado y consejos de salud en personas con lupus eritematoso sistémico. Un estudio descriptivo

García Campos,

Cano García,

al Mashhadani al Mashhadani

et al. 2023

Rev. Esp. Pod.

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Gouty Involvement of Foot and Ankle: Beyond Flares

Cited by 4 publications

References 62 publications

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

Dolor, uso de ortesis plantares, calzado y consejos de salud en personas con lupus eritematoso sistémico. Un estudio descriptivo

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