Integrating the concept of preemptive analgesia with multimodal analgesia.

Cases of mild pain after impacted mandibular third molar extraction.

Celecoxib and tramadol/acetaminophen as effective preemptive adjuvants for pain.

Adverse events unaffected by a single dose of celecoxib or tramadol/acetaminophen.

This study aimed to assess the efficacy and safety of adding single-dose preemptive celecoxib 200 mg (Cc) or tramadol 37.5 mg/acetaminophen 325.0 mg (T/A) to standard postoperative analgesia after impacted mandibular third molar extraction, a design not previously explored.

In this multicenter, prospective, randomized, double-blind, placebo-controlled, crossover within-subject study, participants were randomly assigned to 2 groups (Cc or placebo for group A; T/A or placebo for group B) and underwent impacted mandibular third molar extraction on both sides at 1-month intervals. Along with baseline characteristics, pain intensity in Visual Analogue Scale (VAS), first perceived pain occurrence, rescue medication use, and adverse events were evaluated.

A total of 33 participants per group completed the trial. Cc reduced pain at 3 (−0.91 ± 2.17; P = .011) and 6 hours (−0.85 ± 2.24; P = .018), while T/A reduced pain at 1 (−1.40 ± 2.37; P < .001), 2 (−0.79 ± 2.32; P = .030), and 6 hours (−0.91 ± 1.94; P = .006) postextraction, with some insignificant reductions at other times. Both Cc and T/A were effective in reducing the first perceived pain. Notably, Cc significantly decreased pain intensity, T/A significantly delayed the pain perception. Both drugs had no significant effect on the need for rescue medication or adverse event rates.

Based on these results, both Cc and T/A appears to aid in reducing postoperative pain following impacted mandibular third molar extraction without significant adverse effects.

Preemptive analgesia

Multimodal analgesia

Impacted third molar extraction

Celecoxib

Tramadol/AAP

© 2025 The Authors. Published by Elsevier Inc.