AIM: This study aimed to compare the release of inflammatory mediators and post-operative pain after conservative and conventional root canal preparations of mandibular molars with asymptomatic irreversible pulpitis. METHODOLOGY: Forty-five healthy patients diagnosed with asymptomatic irreversible pulpitis were randomly assigned to three groups based on the system used for root canal preparation (n = 15): ProTaper Gold, OneShape and TruNatomy. Gingival crevicular fluid samples were collected for baseline measurements, 24 and 72 h after root canal treatment. Inflammatory mediators (Substance P, IL-6, IL-10 and PGE-2) were quantified using enzyme-linked immunosorbent assays, and post-operative pain was assessed using the visual analogue scale (VAS) and compared among groups with linear regression analysis. RESULTS: All mediators exhibited an increase at 24 h and a decrease at 72 h. The release of Substance P in the OneShape group was significantly higher than in the TruNatomy and ProTaper Gold groups (Odds Ratio (OR) = 17.4 and 21.7, respectively, at 24 h and 21.5 and 15.6 at 72 h
p <
.05). IL-6 and IL-10 were significantly higher in the OneShape and ProTaper Gold groups compared to TruNatomy at 24 h (p <
.05). PGE2 levels were not affected by the type of instruments (p >
.05). VAS scores were significantly higher at 24 h compared to baseline, with root canal preparation using OneShape significantly associated with higher post-operative pain than preparation with ProTaper Gold (p <
.05). Analgesic intake was not related to the instrumentation group or any other patient- or tooth-related factors. CONCLUSION: Conservative root canal preparation of mandibular molars with asymptomatic irreversible pulpitis decreased the release of inflammatory mediators but did not influence post-operative pain.