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万古霉素对有或无自愿跑步轮使用权的雌性 Fischer 大鼠持续性疼痛刺激和疼痛抑制行为的影响。

Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels.

机构信息

Department of Psychology, University of New England, Biddeford, ME, 04005.

Department of Biomedical Sciences, University of New England College of Osteopathic Medicine, Biddeford, ME, 04005.

出版信息

J Pain. 2021 Nov;22(11):1530-1544. doi: 10.1016/j.jpain.2021.05.003. Epub 2021 May 21.

Abstract

The present experiments determined the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in rats. Persistent inflammatory pain was modeled using dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior, and prevented formalin pain-depressed wheel running. Fecal microbiota transplantation produced a non-significant trend toward reversal of the vancomycin effect on pain-stimulated behavior. Vancomycin depleted Firmicutes and Bacteroidetes populations in the gut while having a partial sparing effect on Lactobacillus species and Clostridiales. The vancomycin treatment effect was associated with an altered profile in amino acid concentrations in the gut with increases in arginine, glycine, alanine, proline, valine, leucine, and decreases in tyrosine and methionine. These results indicate that vancomycin may have therapeutic effects against persistent inflammatory pain conditions that are distal to the gut. PERSPECTIVE: The narrow-spectrum antibiotic vancomycin reduces pain-related behaviors in the formalin model of inflammatory pain. These data suggest that manipulation of the gut microbiome may be one method to attenuate inflammatory pain amplitude.

摘要

本实验旨在研究窄谱抗生素万古霉素对大鼠炎症性疼痛刺激和疼痛抑制行为的影响。采用稀甲醛(0.5%)建立持续性炎症性疼痛模型。两周的口服万古霉素经饮用水给药可减轻第二期福尔马林引起的疼痛刺激行为,并防止福尔马林引起的疼痛抑制轮跑。粪便微生物群移植对万古霉素对疼痛刺激行为的影响有一定的逆转趋势。万古霉素耗尽了肠道中的厚壁菌门和拟杆菌门,而对乳杆菌属和梭菌目有部分保留作用。万古霉素治疗的效果与肠道中氨基酸浓度的改变有关,表现为精氨酸、甘氨酸、丙氨酸、脯氨酸、缬氨酸、亮氨酸增加,而酪氨酸和蛋氨酸减少。这些结果表明,万古霉素可能对远离肠道的持续性炎症性疼痛有治疗作用。观点:窄谱抗生素万古霉素可减少福尔马林诱导的炎症性疼痛模型中的疼痛相关行为。这些数据表明,肠道微生物群的操纵可能是减轻炎症性疼痛幅度的一种方法。

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