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. This evidence concerns the gene TAC1 and periapical periodontitis.