Ramirez Iago, Petean Igor Bassi Ferreira, Paula-Silva Francisco Wanderley Garcia de, Tiballi Aline Aparecida Ferraresi, Sousa-Neto Manoel Damião, Lopes-Olhê Fabiane Carneiro, Leite-Panissi Christie Ramos Andrade, Mazzi-Chaves Jardel Francisco
Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
Arch Oral Biol. 2025 Sep;177:106320. doi: 10.1016/j.archoralbio.2025.106320. Epub 2025 Jun 5.
This study aimed to assess local and central inflammatory aspects, behavioral changes, and alterations in mechanical and nociceptive peripheral sensitivities in a mouse model of experimentally induced pulpitis.
Following Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and ethics committee approval (231.1.395.59.0), 48 wild-type mice (C57BL/6) were allocated into two groups (n = 24): induced pulpitis and control. Pulpitis was induced under anesthesia by accessing the pulp tissue of the right lower first molar and inoculating 10 µL of lipopolysaccharide (LPS) suspension (1 µg/µL). Food intake, water intake, and sucrose at 1 % solution were daily evaluated. Both groups underwent evaluations for mechanical sensitivity (von Frey test) and nociceptive sensitivity (formalin test) at days 2, 5, and 10. Behavior evaluation (open field test) was performed at days 1, 2, 5, and 10. Post-euthanasia, oral tissues (bone and teeth) were collected for histological analysis, and the brain was preserved for Western blotting. Statistical analyses included two-way ANOVA and Fisher's Exact Test (p < 0.05).
Mice with pulpitis showed significantly reduced food consumption on days 2 and 4. Mechanical allodynia was evident in the pulpitis group on days 1 and 2 compared to controls and baseline. Anxious-like behavior was more pronounced in the experimental group (p < 0.05). No significant changes in nociceptive sensitivity were noted (p > 0.05). Histological analysis revealed a higher count of inflammatory cells in the experimental group (p < 0.05). Additionally, increased expression of Nuclear factor kappa B (NF-kB) and Glial fibrillary acidic protein (GFAP) in the amygdaloid complex was observed in the experimental group (p < 0.05).
Experimentally induced pulpitis in mice led to mechanical allodynia and heightened anxious-like behavior, suggesting a potential link between local acute pulpitis and central inflammation via inflammatory marker expression in the amygdaloid complex.
There is consensus in the literature that acute pulpitis disrupts the patient's routine, affecting food and drink consumption, behavior, and causing suffering. However, the link between local inflammation and central inflammatory modulation remains unclear. This study provides insights into how pulp inflammation may affect local and central inflammation, as well as mechanical and peripheral nociceptive sensitivities, emotional changes, and food consumption. It establishes causal relationships, suggesting that central inflammatory stress could be a key factor, potentially guiding new therapeutic approaches based on an animal model.
本研究旨在评估实验性诱导牙髓炎小鼠模型中的局部和中枢炎症情况、行为变化以及机械性和伤害性外周敏感性改变。
遵循《动物研究：体内实验报告》（ARRIVE）指南并获得伦理委员会批准（231.1.395.59.0），将48只野生型小鼠（C57BL/6）分为两组（n = 24）：诱导牙髓炎组和对照组。在麻醉下通过进入右下第一磨牙的牙髓组织并接种10μL脂多糖（LPS）悬液（1μg/μL）诱导牙髓炎。每天评估食物摄入量、饮水量和1%蔗糖溶液摄入量。两组在第2、5和10天进行机械敏感性（von Frey试验）和伤害性敏感性（福尔马林试验）评估。在第1、2、5和10天进行行为评估（旷场试验）。安乐死后，收集口腔组织（骨骼和牙齿）进行组织学分析，并保存大脑用于蛋白质免疫印迹分析。统计分析包括双向方差分析和Fisher精确检验（p < 0.05）。
牙髓炎小鼠在第2天和第4天食物消耗量显著减少。与对照组和基线相比，牙髓炎组在第1天和第2天出现明显的机械性痛觉过敏。实验组的焦虑样行为更为明显（p < 0.05）。未观察到伤害性敏感性有显著变化（p > 0.05）。组织学分析显示实验组炎症细胞计数更高（p < 0.05）。此外，实验组杏仁核复合体中核因子κB（NF-κB）和胶质纤维酸性蛋白（GFAP）的表达增加（p < 0.05）。
实验性诱导的小鼠牙髓炎导致机械性痛觉过敏和焦虑样行为增强，提示局部急性牙髓炎与通过杏仁核复合体中炎症标志物表达的中枢炎症之间存在潜在联系。
文献中一致认为急性牙髓炎会扰乱患者的日常生活，影响饮食摄入、行为并造成痛苦。然而，局部炎症与中枢炎症调节之间的联系仍不清楚。本研究深入探讨了牙髓炎症如何影响局部和中枢炎症，以及机械性和外周伤害性敏感性、情绪变化和食物摄入。它建立了因果关系，表明中枢炎症应激可能是一个关键因素，有可能为基于动物模型的新治疗方法提供指导。
