Effect of simvastatin versus calcium hydroxide intracanal medications on postoperative pain and cytokine modulation in symptomatic apical periodontitis: a randomized controlled trial

Abstract Background Calcium hydroxide has long been used as an intracanal medicament in endodontics and remains widely applied due to its well-established antimicrobial and anti-inflammatory properties. Owing to its clinical effectiveness, it is recommended for use in a variety of endodontic treatment situations. Simvastatin, a drug belonging to the statin class, has demonstrated potential immunomodulatory effects on periapical tissues when administered both locally and systemically. This study aimed to assess the effect of using Simvastatin versus calcium hydroxide Ca(OH)₂ intracanal medicaments on incidence and intensity of postoperative pain and periapical fluid levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) one week post-instrumentation in patients with necrotic mandibular premolars with symptomatic apical periodontitis. Methods Thirty patients diagnosed with single-canaled necrotic premolars, allocated randomly into two groups ( n = 15 each). Root canal therapy was executed across two clinical sessions. Preoperative pain was recorded using the Numeric Rating Scale (NRS). After chemo-mechanical preparation, post-instrumentation periapical fluid (PS-1) was collected. The intervention group received Simvastatin gel, while the control group received Ca(OH)₂ intracanal medication. Participants self-reported pain intensity at 6-, 12-, 24-, and 48-hour intervals post-instrumentation. After one week, a second periapical sample (PS-2) was collected, and both IL-6 and IL-8 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Final obturation was performed using a modified single-cone techniques with bioceramic sealer. Post-obturation pain was similarly documented. Data were statistically analyzed using Mann-Whitney U test for independent samples comparison, Wilcoxon signed rank test for related samples comparison, Friedman test for multiple related samples comparisons followed by Dunn’s post hoc test for pairwise comparison, and Chi square test was used for independent group comparison of categorical data. Results Simvastatin was associated with significantly lower postoperative pain intensity at 6 h post-instrumentation compared to Ca(OH)₂ ( p = 0.037), while no significant differences were observed at other time intervals. The proportion of patients experiencing postoperative pain did not differ significantly between the two groups. Both medications reduced cytokine levels from baseline; however, intergroup comparisons showed no significant differences. Notably, Simvastatin significantly decreased both IL-6 ( p = 0.017) and IL-8 ( p = 0.002) levels, whereas Ca(OH)₂ significantly reduced only IL-8 ( p = 0.005). Conclusions Simvastatin demonstrated comparable efficacy to Ca(OH)₂ in managing postoperative pain and reducing inflammatory mediators, suggesting its potential as an alternative intracanal medication. While Ca(OH)₂ remains the gold standard intracanal medicament, simvastatin demonstrated promising anti-inflammatory effects that may contribute to reduced postoperative pain and decreased levels of pro-inflammatory mediators. Future investigations incorporating larger sample sizes, extended follow-up durations, different simvastatin concentrations, alternative delivery vehicles, long-term radiographic healing outcomes, effect on other inflammatory mediators, and its applicability in different types of apical periodontitis or retreatment cases are essential to corroborate these outcomes and evaluate the expanded clinical utility of simvastatin within endodontic therapy. Trial registration The trial was registered at clinicaltrials.gov with Registration number: NCT 05525013. (CEBD-CU-2022-8-30)