Differential Regulation of Angiogenesis, Lymphangiogenesis, and Neural Tissue in Normal and Inflamed Dental Pulp:...

Background/Objectives: Pulp inflammation impairs healing, yet the underlying vascular and neural mechanisms remain poorly understood. This study investigated the differential regulation of lymphatic vessels, blood vessels, and neural tissue in pulpitis to elucidate healing limitations in inflamed dental pulp. Methods: This study evaluated 38 pulp samples (14 symptomatic irreversible pulpitis, 13 asymptomatic irreversible pulpitis, and 11 healthy controls) via immunohistochemistry, using D2-40 to identify lymphatic vessels, CD31 to mark blood vessels, and PGP9.5 to detect neural tissue. Vessel counts and neural tissue scoring were performed by blinded examiners and analyzed using appropriate statistical tests. Results: Dental pulp with symptomatic irreversible pulpitis exhibited significantly increased blood vessel density (50.3 vs. 39.2 in asymptomatic irreversible pulpitis and 25.8 in controls, p = 0.001, Cohen's d = 1.82), while lymphatic vessel density remained unchanged across all groups (p ≥ 0.05), indicating impaired lymphangiogenesis despite inflammation. Neural tissue density was consistent across conditions, with a significant negative correlation between PGP9.5 expression and age (r = -0.5, p = 0.001). CD31 and D2-40 expression showed a positive correlation (r = 0.389, p = 0.016), suggesting coordinated vascular development. Conclusions: Our findings reveal a critical imbalance between enhanced angiogenesis and impaired lymphangiogenesis during pulpitis, potentially explaining the compromised healing capacity of inflamed dental pulp. This vascular dysregulation, combined with persistent neural tissue density, creates an environment in which inflammatory exudates accumulate with limited clearance. These insights indicate a need for new therapeutic strategies aimed at enhancing lymphangiogenesis to improve endodontic outcomes.