Preoperative Pain Intensity, Chronicity, and Referral as Predictors of Postoperative Complications in Impacted Third Molar Surgery: A Systematic Review and Meta-Analysis

Background: Impacted third molar extraction is one of the most frequently performed oral surgical procedures and is commonly associated with postoperative complications, including pain, alveolar osteitis, neurosensory injury, delayed mucosal healing, trismus, and swelling. These sequelae substantially affect patient recovery and healthcare utilization. Preoperative pain characteristics—intensity, chronicity, referral patterns, and aetiology—may predict these complications, potentially mediated by neuroinflammatory and sensitization mechanisms. However, evidence remains inconsistent due to variation in study designs and pain assessments. Objective: To systematically review and meta-analyse the predictive value of preoperative pain intensity, chronicity, referral patterns, and aetiology for postoperative complications in impacted third molar surgery, synthesising prospective data up to June 2025 to inform risk stratification and perioperative management. Methods: This review followed PRISMA 2020 guidelines and was registered on PROSPERO (CRD420251123273). Comprehensive searches were conducted in PubMed, Embase, Scopus, Cochrane CENTRAL, Web of Science, and grey literature (Google Scholar, ClinicalTrials.gov) to June 30, 2025. Eligible studies were prospective cohort studies or randomised controlled trials (RCTs) assessing preoperative pain with validated tools (Visual Analog Scale [VAS] or Numeric Rating Scale [NRS]) in patients aged ≥16 years undergoing third molar extraction, with ≥7 days of follow-up. Primary outcomes were postoperative pain (VAS/NRS at 24 h, 72 h, 7 d, and 14 d), alveolar osteitis, nerve injury, and mucosal healing time. Secondary outcomes included trismus, swelling, and quality of life (Oral Health Impact Profile [OHIP-14]). Random-effects meta-analyses calculated standardised mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for binary outcomes with 95% confidence intervals (CIs) and I² for heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale (NOS) for cohorts and Cochrane RoB 2 for RCTs. Certainty of evidence was graded with GRADE. Results: From 3,456 records, 28 studies (18 cohorts, 10 RCTs; n=10,832 patients) were included. Severe preoperative pain (VAS >60 mm) was associated with higher postoperative pain at 7 days (SMD 0.78, 95% CI 0.62–0.94; I²=65%; 22 studies; p<0.001). Chronic pain (≥3 months) increased the risk of alveolar osteitis (RR 1.68, 95% CI 1.35–2.09; I²=50%; 20 studies; p<0.001) and delayed mucosal healing (mean difference 3.8 days, 95% CI 2.5–5.1; I²=70%; 12 studies; p<0.001). Referred pain significantly raised nerve injury risk (RR 2.05, 95% CI 1.28–3.27; I²=45%; 15 studies; p=0.003). Stronger effects were observed in younger patients (16–19 years: SMD 0.85 vs. ≥30 years: SMD 0.65; p=0.04). Sensitivity analyses lowered heterogeneity (I²=48%; SMD 0.70). Publication bias was minimal (Egger’s p=0.18). Conclusion: Preoperative pain characteristics are strong predictors of complications following third molar surgery. Standardised VAS/NRS assessments, multimodal analgesia for severe pain, nerve-sparing techniques in patients with referred pain, and extended monitoring in those with chronic pain are recommended. Future research should standardise protocols and evaluate targeted interventions.