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通过在LOU/C/Jall和Sprague-Dawley老年大鼠中诱导的MI-RAT©骨关节炎模型比较疼痛表达及其与肠道微生物群的关联。

Comparative Pain Expression and Its Association to Intestinal Microbiota Through the MI-RAT© Osteoarthritis Model Induced in LOU/C/Jall and Sprague-Dawley Aged Rats.

作者信息

Frézier Marilyn, Otis Colombe, Labelle Emilie, Lussier Bertrand, Gaudreau Pierrette, Authier Simon, Costa Marcio Carvalho, Beaudry Hélène, Troncy Eric

机构信息

Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Université de Montréal, St.-Hyacinthe, QC J2S 2M2, Canada.

Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC H2X 0A9, Canada.

出版信息

Int J Mol Sci. 2025 Aug 8;26(16):7698. doi: 10.3390/ijms26167698.

DOI:10.3390/ijms26167698
PMID:40869019
Abstract

To investigate the involvement of gut-brain axis in musculoskeletal chronic pain in the elderly, this preclinical study aimed to compare osteoarthritis (OA) pain expression, cognitive function and gut microbiota composition in two aging rat strains (11-15 months). A validated surgically induced OA model was used in Sprague-Dawley (SD; = 12), as standard group, and in LOU/C/Jall rats (LOU; = 8), a healthy aging model. The OA pain response was assessed longitudinally (60 days) through quantitative sensory testing (mechanical sensitization and endogenous inhibitory control functionality), spatial memory, and gut microbiota. At sacrifice, joint structural alterations and spinal neuropeptides concentrations were quantified. After OA induction, higher mechanical hypersensitivity in LOU than in SD was also associated with higher endogenous inhibitory control ( < 0.05). Expression of pro-/anti-nociceptive spinal neuropeptides, cognitive function and joint alterations were similar in both groups. Gut microbiota composition was different ( < 0.001) and different taxa were associated with each strain (e.g., spp. with LOU vs. spp. with SD). This study suggests healthy aging to be associated with more efficient endogenous pain control and expression of specific intestinal bacteria. This research questions the implication of the intestinal microbiota in aging and chronic pain control.

摘要

为研究肠-脑轴在老年人肌肉骨骼慢性疼痛中的作用,这项临床前研究旨在比较两种老龄大鼠品系(11 - 15个月)的骨关节炎(OA)疼痛表现、认知功能和肠道微生物群组成。在标准组的Sprague-Dawley(SD;n = 12)大鼠以及健康老龄模型的LOU/C/Jall大鼠(LOU;n = 8)中使用了经过验证的手术诱导OA模型。通过定量感觉测试(机械性致敏和内源性抑制控制功能)、空间记忆和肠道微生物群对OA疼痛反应进行纵向评估(60天)。在处死时,对关节结构改变和脊髓神经肽浓度进行定量分析。OA诱导后,LOU大鼠比SD大鼠具有更高的机械性超敏反应,这也与更高的内源性抑制控制相关(P < 0.05)。两组中促/抗伤害感受性脊髓神经肽的表达、认知功能和关节改变相似。肠道微生物群组成不同(P < 0.001),不同的分类群与每个品系相关(例如,LOU大鼠与spp.相关,SD大鼠与spp.相关)。这项研究表明健康老龄与更有效的内源性疼痛控制和特定肠道细菌的表达有关。该研究对肠道微生物群在衰老和慢性疼痛控制中的作用提出了质疑。

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本文引用的文献

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HGF Aggravated Periodontitis-Associated Gut Barrier and Microbial Dysfunction: Implications for Oral-Gut Axis Regulation.肝细胞生长因子加重牙周炎相关的肠道屏障和微生物功能障碍:对口腔-肠道轴调节的影响。
Biology (Basel). 2025 May 2;14(5):496. doi: 10.3390/biology14050496.
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Inflammaging contributes to osteoarthritis development and human microbiota variations and vice versa: A systematic review.炎症衰老促进骨关节炎的发展和人类微生物群的变化,反之亦然:一项系统综述。
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Predictive and concurrent validity of pain sensitivity phenotype, neuropeptidomics and neuroepigenetics in the MI-RAT osteoarthritic surgical model in rats.
大鼠MI-RAT骨关节炎手术模型中疼痛敏感性表型、神经肽组学和神经表观遗传学的预测效度与同时效度
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The Effect of Probiotics on the Management of Pain and Inflammation in Osteoarthritis: A Systematic Review and Meta-Analysis of Clinical Studies.益生菌对骨关节炎疼痛和炎症管理的影响:临床研究的系统评价和荟萃分析。
Nutrients. 2024 Jul 12;16(14):2243. doi: 10.3390/nu16142243.
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Vet J. 2024 Apr;304:106102. doi: 10.1016/j.tvjl.2024.106102. Epub 2024 Mar 16.
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