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基孔肯雅病毒颗粒和RNA以TRPV1依赖的方式诱导机械性和热超敏反应。

Chikungunya Particle and RNA Induce Mechanical and Heat Hypersensitivities in a TRPV1-Dependent Manner.

作者信息

da Silva Liziane C M, Dos Santos Maia Andressa C, de Sousa Nágila C F, Pavi Catielen P, Savi Beatriz P, Nagashima Seigo, Damasceno Samara, Schneider Ayda H, Mascarin Lucas Z, Rodrigues João F S, Monteiro Cinara R A V, Silva Izabella T, Fongaro Gislaine, Monteiro-Neto Valério, Bomfim Maria R Q, Cunha Thiago M, de Sousa Valente João, Calixto João B, de Noronha Lúcia, Brain Susan D, Fernandes Elizabeth S

机构信息

Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil.

Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil.

出版信息

Biomolecules. 2025 Jan 23;15(2):171. doi: 10.3390/biom15020171.

DOI:10.3390/biom15020171
PMID:40001474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11853433/
Abstract

Chikungunya virus (CHIKV), the causative agent of the chikungunya fever, is an alphavirus widely transmitted by the bite of the female mosquito of the genus sp., especially in tropical and subtropical regions. Brazil is the country most affected by the microorganism. CHIKV classically induces articular pain, which can become long lasting for even years in a great number of the infected individuals, reducing their quality of life. The mechanisms of CHIKV-induced pain are poorly understood, but recent evidence indicated a role for the transient receptor potential vanilloid 1 (TRPV1) in this pathology. Herein, we assessed the ability of intra-articularly injected inactivated CHIKV or its RNA to trigger nociception in mice. Both stimuli induced bilateral secondary hyperalgesia to mechanical and heat stimuli. These responses were attenuated by TRPV1 ablation or antagonism. Joint structural alterations and increased cartilage TRPV1 protein expression were detected in the ipsilateral knee joints injected with either CHIKV or viral RNA. However, the lack of this receptor did not influence the histological changes triggered by CHIKV or RNA. The results further support the role of TRPV1 in CHIKV-induced pain and highlight its importance in the chronic phase of the disease.

摘要

基孔肯雅病毒(CHIKV)是基孔肯雅热的病原体,属于甲病毒属,主要通过 属雌性蚊子叮咬传播,在热带和亚热带地区尤为常见。巴西是受该微生物影响最严重的国家。传统上,CHIKV会引发关节疼痛,许多感染者的疼痛可持续数年,严重影响生活质量。目前对CHIKV引发疼痛的机制了解甚少,但最近有证据表明瞬时受体电位香草酸受体1(TRPV1)在这一病理过程中发挥作用。在此,我们评估了关节内注射灭活CHIKV或其RNA引发小鼠伤害感受的能力。两种刺激均诱发了对机械和热刺激的双侧继发性痛觉过敏。这些反应可通过TRPV1基因敲除或拮抗剂减弱。在注射CHIKV或病毒RNA的同侧膝关节中,检测到关节结构改变和软骨TRPV1蛋白表达增加。然而,缺乏该受体会不会影响CHIKV或RNA引发的组织学变化。这些结果进一步支持了TRPV1在CHIKV引发疼痛中的作用,并突出了其在疾病慢性期的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/4db3cd7b5f6c/biomolecules-15-00171-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/e0dc5f18a360/biomolecules-15-00171-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/92dfacbc79da/biomolecules-15-00171-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/d354be4647f6/biomolecules-15-00171-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/45b51b8d9fb7/biomolecules-15-00171-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/4db3cd7b5f6c/biomolecules-15-00171-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/e0dc5f18a360/biomolecules-15-00171-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/92dfacbc79da/biomolecules-15-00171-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/d354be4647f6/biomolecules-15-00171-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/45b51b8d9fb7/biomolecules-15-00171-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b12/11853433/4db3cd7b5f6c/biomolecules-15-00171-g005.jpg

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本文引用的文献

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Targeting TRP channels for pain relief: A review of current evidence from bench to bedside.靶向 TRP 通道缓解疼痛:从实验室到临床的现有证据综述。
Curr Opin Pharmacol. 2024 Apr;75:102447. doi: 10.1016/j.coph.2024.102447. Epub 2024 Mar 11.
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Transient receptor potential vanilloid 1: A potential therapeutic target for the treatment of osteoarthritis and rheumatoid arthritis.
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Inflammation, fibrosis and E1 glycoprotein persistence in joint tissue of patients with post-Chikungunya chronic articular disease.关节组织中持续性 E1 糖蛋白与炎症、纤维化及基孔肯雅热慢性关节病的关系。
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The role of TRPV1 in RA pathogenesis: worthy of attention.TRPV1 在 RA 发病机制中的作用:值得关注。
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Kinins' Contribution to Postoperative Pain in an Experimental Animal Model and Its Implications.激肽在实验动物模型中对术后疼痛的作用及其意义
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Chikungunya Virus and Its Envelope Protein E2 Induce Hyperalgesia in Mice: Inhibition by Anti-E2 Monoclonal Antibodies and by Targeting TRPV1.基孔肯雅病毒及其包膜蛋白 E2 诱导小鼠痛觉过敏:抗 E2 单克隆抗体和靶向 TRPV1 的抑制作用。
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