ObjectiveThis study aimed to investigate the associations between serum inflammatory mediators and chronic pain after laparoscopic inguinal hernia repair in elderly patients.MethodsFrom March 2022 to June 2023, 116 elderly patients (≥65 years old) diagnosed with inguinal hernia were enrolled in this study. All patients underwent total extraperitoneal repair (TEP) by laparoscopic surgery. Blood samples were obtained from each patient within the first postoperative day. Serum profiles of IL-1β, IL-6, IL-18, HMGB1, and NLRP3 were determined by ELISA. After that, a 6-month follow-up was performed, and pain was assessed using the Visual Analog Scale (VAS). Chronic pain was defined as inguinal pain that persisted for at least 6 months. On the basis of this definition, patients were divided into a chronic pain group (CP group, n = 11) and a non-chronic pain group (Non-CP group, n = 105). Logistic regression analysis was applied to investigate significant predictors of postoperative chronic pain, and the predictive performance of related indicators was verified using receiver operating characteristic (ROC) curves.ResultsUnivariate logistic analysis revealed that the presence of diabetes, hernia ring defect diameter, severe hernia ring adhesions, prolonged time to resume daily activities, and recurrence of hernia were significantly associated with postoperative chronic pain (all p < 0.05). Additionally, serum indicators, including elevated neutrophil counts and serum levels of IL-1β, IL-6, CRP, HMGB1, and NLRP3, were elevated in patients with postoperative chronic pain (all p < 0.05). Multivariate logistic regression analysis revealed that IL-6 (OR = 1.99, 95% CI 1.28–3.10; p = 0.002) and NLRP3 (OR = 1.39, 95% CI 1.14–1.69; p = 0.001) independently predict increased risk factors for chronic pain. The results of the ROC curve revealed that elevated IL-6 and NLRP3 levels had excellent predictive value for chronic pain, with AUCs of 0.975 (95% CI 0.949–1.000) and 0.907 (95% CI 0.852–0.961), respectively.ConclusionHernia ring defect diameter and early postoperative serum levels of IL-6 and NLRP3 are independent risk factors for chronic pain after TEP in elderly patients. IL-6 and NLRP3 are promising exploratory candidate biomarkers that warrant further validation.