IL-33/ST2 signaling in pain and itch: Cellular and molecular mechanisms and therapeutic potentials

Li, Peiyi; Yu, Qilin; Nie, Huimin; Yin, Chengyu; Liu, Boyi

doi:10.1016/j.biopha.2023.115143

Cited by 8 publications

(3 citation statements)

References 84 publications

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“…Furthermore, ROS is indispensable for MSU-induced NLRP3 inflammasome activation 56 . There are studies showing that ROS are generated from the inflamed joint tissues of gouty arthritis model animals 13 , 57 , 58 . Antioxidants are able to reduce NLRP3 inflammasome activation via decreasing ROS overproduction in the inflamed joint tissues of gouty arthritis model animals 12 .…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Glial cells, which are nonneuronal cells responsible for supporting and protecting neurons in both the central and peripheral nervous systems, play a significant role in this context. The close proximity of satellite glial cells to neuronal cell bodies facilitates interactions via paracrine signaling, thereby contributing to the sensitization of afferent neurons (Davies et al, 2020; Li, Yu, et al, 2023). Herein, peripheral sensitization refers to an increased sensitivity of nociceptive neurons (pain‐sensing neurons) to incoming signals.…”

Section: The Pathogenesis Of Npmentioning

confidence: 99%

Treatment of neuropathic pain by traditional Chinese medicine: An updated review on their effect and putative mechanisms of action

Guo,

Zhang,

Feng

2024

Phytotherapy Research

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Neuropathic pain (NP) is a common chronic pain with heterogeneous clinical features, and consequent lowering of quality of life. Currently, although conventional chemical drugs can effectively manage NP symptoms in the short term, their long‐term efficacy is limited, and they come with significant side effects. In this regard, traditional Chinese medicine (TCM) provides a promising avenue for treating NP. Numerous pharmacological and clinical studies have substantiated the effectiveness of TCM with multiple targets and mechanisms. We aimed to outline the characteristics of TCM, including compound prescriptions, single Chinese herbs, active ingredients, and TCM physical therapy, for NP treatment and discussed their efficacy by analyzing the pathogenesis of NP. Various databases, such as PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang database, were searched. We focused on recent research progress in NP treatment by TCM. Finally, we proposed the future challenges and emerging trends in the treatment of NP. TCM demonstrates significant clinical efficacy in NP treatment, employing multi‐mechanisms. Drawing from the theory of syndrome differentiation, four types of dialectical treatments for NP by compound TCM prescriptions were introduced: promoting blood circulation and removing blood stasis; promoting blood circulation and promote Qi flow; warming Yang and benefiting Qi; soothing the liver and regulating Qi. Meanwhile, 33 single Chinese herbs and 25 active ingredients were included. In addition, TCM physical therapy (e.g., acupuncture, massage, acupoint injection, and fumigation) also showed good efficacy in NP treatment. TCM, particularly through the use of compound prescriptions and acupuncture, holds bright prospects in treating NP owing to its diverse holistic effects. Nonetheless, the multi‐targets of TCM may result in possible disadvantages to NP treatment, and the pharmacological mechanisms of TCM need further evaluation. Here, we provide an overview of NP treatment via TCM, based on the pathogenesis and the potential therapeutic mechanisms, thus providing a reference for further studies.

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“…Tissueresident macrophages engulf MSU via phagocytosis and release a panel of cytokines or chemokines (e.g., IL-1β, TNF-α) [9][10][11] . These cytokines or chemokines drive neutrophil recruitment in the joint, which is a hallmark of acute gout arthritis 12,13 . The influx of neutrophils into joints can release ROS and inflammatory mediators that further contribute to pain and tissue damage 12,14,15 .…”

mentioning

confidence: 99%

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis

Yin,

Liu,

Dong

et al. 2024

Nat Commun

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Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation. CXCL5 expression was increased in ankle joints of gout arthritis model mice, whereas CXCR2 showed expression in joint-innervating sensory neurons. CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to trigger TRPA1 activation, resulting in hyperexcitability and pain. Neuronal CXCR2 coordinates with neutrophilic CXCR2 to contribute to CXCL5-induced neutrophil chemotaxis via triggering CGRP- and substance P-mediated vasodilation and plasma extravasation. Neuronal Cxcr2 deletion ameliorates joint pain, neutrophil infiltration and gait impairment in model mice. We confirmed CXCR2 expression in human dorsal root ganglion neurons and CXCL5 level upregulation in serum from male patients with gouty arthritis. Our study demonstrates CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and inflammation that expands our knowledge of immunomodulation capability of nociceptive sensory neurons.

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IL-33/ST2 signaling in pain and itch: Cellular and molecular mechanisms and therapeutic potentials

Cited by 8 publications

References 84 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

Treatment of neuropathic pain by traditional Chinese medicine: An updated review on their effect and putative mechanisms of action

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis

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