# Anti-Inflammatory Effect of Resiniferatoxin During Gingival Tissue Inflammation After Mechanical Pulp Damage in a Murine Experimental Model

## TL;DR

This study shows that resiniferatoxin reduces inflammation in mouse gums after tooth pulp damage, similar to common drugs like ibuprofen.

## Contribution

The novel contribution is demonstrating resiniferatoxin's anti-inflammatory efficacy in a murine model of pulp-induced gingival inflammation.

## Key findings

- Resiniferatoxin significantly reduced plasma PGE2 and TNF-α levels after pulp damage.
- Resiniferatoxin decreased inflammatory cell infiltration in gingival tissue.
- Its anti-inflammatory effects were comparable to ibuprofen and dexamethasone.

## Abstract

Gingival inflammation represents one of the most prevalent oral inflammatory conditions worldwide and remains a major contributor to oral morbidity. While its classical etiologies are well established, less attention has been paid to inflammatory responses that arise secondary to pulpal injury and tissue damage. Experimental models that allow controlled evaluation of these responses may provide relevant insight into pulp-associated gingival inflammatory processes. Current pharmacological approaches for inflammatory conditions in dentistry, including non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, are widely used and generally effective. However, their use may be associated with adverse effects in specific clinical contexts, particularly under prolonged or high-dose regimens, highlighting the importance of continued investigation of additional pharmacological strategies. Within this context, pharmacological modulation of inflammatory pathways represents a relevant strategy for exploring alternative therapeutic approaches in pulp-associated gingival inflammation. Accordingly, there is a need to investigate novel molecules with therapeutic potential, such as resiniferatoxin, which has demonstrated anti-inflammatory properties in both in vitro and in vivo experimental models. This study aims to evaluate the anti-inflammatory effect of resiniferatoxin during inflammation of gingival tissue after mechanical pulp damage in a murine experimental model. Six groups of six BALB/c mice were formed as follows: five control groups: a healthy group (HCG), a healthy group treated with resiniferatoxin (RTXHG), a group with pulp damage at 14 h (PGI), two groups with pulp damage treated with ibuprofen (PGIIBU), dexamethasone (PGIDEX) at 14 h, and an experimental group with pulp damage treated with resiniferatoxin (PGIRTX) at 14 h. Gingival inflammation was evaluated after pulp damage was induced through mechanical pulp exposure of the upper first molar. The histopathological parameters of the gingival tissue of all groups were evaluated by hematoxylin and eosin (H&E) staining, while the plasma levels of PGE2 and TNF-α were quantified by ELISA assay. A significant increase in plasma PGE2 and TNF-α levels was observed at 14 h after pulp damage. Subsequently, when treatment with resiniferatoxin was administered, it was observed that this significantly decreased (* p < 0.05) the plasmatic levels of PGE2 and TNF-α, as well as the number of inflammatory cells infiltrated in the gingival tissue 14 h after the pulp damage, similar to treatments with ibuprofen and dexamethasone. Resiniferatoxin exerts an anti-inflammatory effect after pulp damage, significantly decreasing plasma levels of PGE2 and TNF-α, as well as the number of inflammatory cells infiltrated in the gingival tissue, which places resiniferatoxin as a potential drug, in this case, for the treatment of gingival inflammation.