Comparative Evaluation of Herbal and Conventional Endodontic Irrigants on Postoperative Pain and Substance P Levels in Patients With Symptomatic Irreversible Pulpitis and Apical Periodontitis

Introduction Postoperative pain is a common complication following root canal treatment (RCT) in teeth with symptomatic irreversible pulpitis and apical periodontitis. This study aimed to compare the effects of ketorolac tromethamine, 100% <i>Moringa oleifera</i> leaf extract, 50% <i>Azadirachta indica</i> leaf extract, and 5.25% sodium hypochlorite, as final root canal irrigants, on postoperative pain intensity and Substance P expression in patients with symptomatic irreversible pulpitis and apical periodontitis. Materials and methods In this prospective observational study, 84 patients with maxillary or mandibular molars diagnosed with symptomatic irreversible pulpitis and apical periodontitis were divided into four groups (21 patients each) based on the final irrigant used during single-visit RCT. Preoperative and postoperative Substance P levels were measured in pulp and periapical blood/exudate samples using enzyme-linked immunosorbent assay (ELISA). Pain intensity was assessed preoperatively and 24 hours postoperatively using a visual analog scale (VAS). Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, one-way analysis of variance (ANOVA), Kruskal-Wallis tests, post-hoc comparisons, and Pearson correlation. Results All irrigants were associated with significant intragroup reductions in both Substance P levels and pain intensity at 24 hours (p = 0.001). Preoperative Substance P levels showed significant intergroup differences, which largely resolved postoperatively. Postoperative pain scores differed significantly between groups, with <i>A. indica</i> being associated with higher pain than the other three irrigants, which demonstrated comparable outcomes. No consistent correlation was found between Substance P levels and pain scores. Conclusion All tested irrigants effectively reduced postoperative pain and Substance P expression. Sodium hypochlorite, ketorolac tromethamine, and <i>M. oleifera</i> leaf extract provided similar analgesic efficacy, which was superior to that of <i>A. indica</i>. Alternative irrigants may serve as viable adjuncts in clinical practice, particularly when enhanced biocompatibility or anti-inflammatory effects are desired.