Decoding signaling crosstalk in pulpitis: pathogenesis and precision therapeutics

Irreversible pulpitis presents a complex pathological challenge, marked by severe inflammation within the low-compliance dentin chamber. Its progression to pulpal necrosis is governed by intricate molecular interactions. Hyperactivation of the TLR/NF-κB and MAPK pathways triggers a pro-inflammatory cascade, while HIF-1α accumulation under hypoxic conditions induces significant metabolic reprogramming. Meanwhile, the NLRP3 inflammasome exacerbates tissue damage by promoting programmed cell death. Endogenous Wnt/β-catenin and TGF-β/Smad signaling pathways strive to promote structural repair and dentinogenesis, but are often suppressed by the hyperactive inflammatory environment. Recent translational research highlights the potential of targeted molecular interventions to address this pathological imbalance. This review synthesizes emerging therapeutic strategies aimed at these key pathways, emphasizing the pharmacological use of specific phytochemicals, epigenetic regulators, and specialized pro-resolving mediators, particularly Resolvin E1, which collaboratively attenuate NF-κB-driven inflammation while enhancing Wnt- and TGF-β-mediated regenerative processes. Additionally, this review discusses the development of next-generation, microenvironment-responsive biomaterials designed to adapt dynamically to pulpal hypoxia and oxidative stress. Ultimately, understanding these signaling interactions lays a molecular foundation for advancing objective, biomarker-based diagnostics and precision therapeutics, offering promising prospects for predictable vital pulp therapy.