BackgroundDentin hypersensitivity, often occurring after dental treatments or from erosive lesions, is a prevalent patient complaint. This study introduces a paste combining 8% L-arginine, calcium carbonate, and potassium nitrate to evaluate its impact on dentinal tubules occlusion, dentin permeability, and tooth sensitivity.MethodsDentin surfaces from 24 third molars (thickness: 2 mm) were divided into two groups of 12. One received the experimental paste, while the other received a placebo without desensitizer. Permeability and sealing ability were assessed through scanning electron microscopy (SEM) and dentin permeability measurement. The pastes’ effects on hypersensitivity were then examined in a triple-blind, randomized parallel-armed clinical trial with 16 eligible patients. Sensitivity to cold, touch, and spontaneous stimuli was recorded using the VAS scale at various intervals post-treatment. Statistical analysis was conducted using Shapiro-Wilk, Mann-Whitney U, Friedman, and Wilcoxon tests (α = 0.05).ResultsThe permeability test demonstrated a significant reduction in dentin permeability in the experimental group (P = 0.002) compared to the control (P = 0.178). SEM images revealed most dentinal tubules in the intervention samples to be occluded. Clinically, both groups showed a significant decrease in the three types of evaluated sensitivity throughout the study. However, no significant difference in sensitivities between the two groups was observed, with the exception of cold sensitivity at three months post-treatment (P = 0.054).ConclusionThe innovative desensitizing paste featuring 8% L-arginine, calcium carbonate, and potassium nitrate effectively occluded dentinal tubules and reduced dentin permeability. It mitigated immediate and prolonged dentin hypersensitivity to various stimuli, supporting its potential role in managing dentin hypersensitivity.Trial registrationhttp://irct.ir: IRCT20220829055822N1, September 9th, 2022.