Effect of chronic unpredictable stress on the progression of experimental apical periodontitis in rats

Abstract Aim To establish an experimental model combining chronic stress and apical periodontitis by assessing the development of periapical lesions in rats in three different time points. Methodology Forty‐eight male Wistar rats were randomly assigned into two equal groups: Apical periodontitis (AP) and AP + Stress (AP + S). The animals of the AP group were not exposed to stressful conditions whereas the AP + S group were exposed to a variety of stressors on a daily basis until the end of the experiment. After three weeks of chronic unpredictable stress, apical periodontitis was induced in both groups by exposing the pulpal tissue of the mandibular first molar to the oral environment. Each group was further subdivided into three subgroups according to the euthanasia period: 14, 21 and 28 days after pulp exposure. The animals were weighed, and the blood was collected for corticosterone serum dosage by radioimmunoassay. The mandibles were removed and submitted to histopathological and microtomography analyses to assess the inflammatory response and the progression of periapical lesions. Comparisons between the AP and AP + S groups were performed using Student’s t ‐test and Mann–Whitney U ‐test for parametric and nonparametric data, respectively. The one‐way anova test followed by Tukey’s test (parametric data) and Kruskal–Wallis followed by Dunn’s test (nonparametric data) were used for comparisons between the three time points within the same group ( P < 0.05). Results The AP + S group had a significantly lower average percentage of weight gain at 14 days and 21 days after AP induction ( P < 0.05). Significantly higher levels of corticosterone were found in the AP + S group at 21 days ( P < 0.05). The AP + S group had a significantly greater intensity and extension of inflammatory infiltrate with larger areas of bone loss compared to the AP groups at 21 days ( P < 0.05). The volume of the periapical lesions in the AP + S group was significantly larger than that of the AP group 21 days following pulp exposure ( P < 0.05). Conclusions The chronic unpredictable stress model applied for 6 weeks exacerbated the inflammatory response and increased bone loss associated with AP, especially 21 days after its induction. This model appears to be suitable for investigating the bidirectional relationship between apical periodontitis and chronic stress.