Multifactorial Analysis of Post-Operative Pain Resolution in Root-End Resection Surgery

Abstract

Root-end resection surgery effectively manages persistent periapical pathosis, yet post-operative pain experiences vary significantly among patients. While demographic, clinical, and psychological risk factors for chronic post-surgical pain are recognized in medicine, the risk factors involving dental surgeries are limited. This thesis aimed to comprehensively characterize clinical, psychosocial, and biological predictors of acute, sub-acute, and persistent post-operative pain following endodontic microsurgery. A prospective cohort study of 93 patients undergoing root-end resection surgery was conducted. Pre-, intra-, and post-operative data were collected on demographic, medical, and dental history, psychological variables, perioperative pain history, and surgery-related variables. Acute pain intensity was monitored daily for 7 days post-surgery, with long-term follow-ups at 1, 3, and 6 months. Gingival crevicular fluid (GCF) was collected from the diseased teeth and healthy control teeth preoperatively, at 1-week, and 6 months to quantify 10 pro-inflammatory cytokines. Data were analyzed using latent class mixed modeling (LCMM) for pain trajectories, Ordered Probit Gaussian Process (OPGP) modeling for biological predictive performance, and multivariate logistic regression. Acute post-operative pain resolution was investigated, where LCMM identified two distinct pain trajectory groups: resolving (85%) and non-resolving (15%). High Pain Catastrophizing Scale (PCS) scores, pre-existing chronic bodily pain, and pre-operative surgical site pain were significant predictors of non-resolving acute post-operative pain. GCF cytokine profiling revealed a localized spike in all 10 cytokines at 1-week post-surgery. OPGP modeling demonstrated that average peri-operative cytokine levels provided the strongest predictive performance for acute pain resolution compared to clinical covariates. Specifically, IL-2, IL-6, IL-8, and IL-13 were positive estimators of prolonged acute pain, whereas TNF-α was a negative estimator. Extending the timeline to evaluate long-term outcomes revealed that 16% of patients developed persistent chronic post-surgical pain (CPSP). Persistent pain was significantly predicted by pre-operative tenderness to palpation and high somatization scores. Furthermore, patients with persistent pain sustained elevations of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) at 6 months, indicating prolonged localized immune dysregulation. Post-operative pain resolution following endodontic microsurgery is a highly multifactorial process affected by perioperative, psychological, and biological factors. Integrating comprehensive assessments with localized GCF biomarkers enables clinicians to design more personalized and precise pain management strategies for endodontic patients.