Is dental pulp inflammation capable of causing central inflammation, behavioral, and sensory alterations? A pre-clinical study

Abstract

Objective

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.

Design

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).

Results

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).

Conclusions

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.

Clinical relevance

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.