Abstract
BACKGROUND: Pulpitis is a common oral inflammatory condition driven by bacterial infection, immune imbalance, and oxidative stress, often involving pro-inflammatory cell death within the dental pulp. Necroptosis-a regulated, caspase-independent form of cell death mediated by the receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL)-has garnered growing interest in various infectious and inflammatory diseases. However, its specific role in pulpitis remains underexplored. AIM OF THE STUDY: This review aims to explore how bacterial infection, immune imbalance, and oxidative stress synergistically activate necroptosis, and proposes for the first time that excessive activation of necroptosis may contribute to the progression of pulpitis. METHODOLOGY: A narrative review was conducted using PubMed, Web of Science, and Google Scholar. Searches employed the keywords "pulpitis", "necroptosis", and related MeSH terms, combined with Boolean operators. RESULTS: Based on a comprehensive review of the existing literature, this review is the first to propose that the integration of bacterial infection, immune imbalance, and oxidative stress may contribute to the progression of pulpitis from reversible inflammation to irreversible necrosis. CONCLUSION: Bacterial infection in pulpitis may activate necroptosis through the Toll-Like Receptor 4 (TLR4)-RIPK3 pathway, leading to the release of damage-associated molecular patterns (DAMPs) that disrupt immune homeostasis, while mitochondrial dysfunction-induced ROS further aggravates oxidative stress. These interacting mechanisms may collectively exacerbate pulpal inflammation and tissue damage, ultimately resulting in irreversible pulpitis. Accordingly, targeting necroptosis pathways may offer a promising therapeutic approach for pulpitis.