Effect of COMT gene polymorphism on post-thoracotomy pain and analgesic requirements in patients receiving multimodal pre-emptive analgesia with pregabalin versus naproxen: A randomized clinical trial

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Objective: To evaluate the association between catechol-O-methyltransferase (COMT) gene polymorphism and postoperative pain intensity and rescue analgesic requirements in thoracotomy patients receiving pre-emptive pregabalin versus naproxen. Methods: In this prospective randomized trial, 40 ASA I–II adults undergoing elective thoracotomy were randomized to pre-emptive oral pregabalin (2.5 mg/kg, n = 20) or naproxen (7 mg/kg, n = 20). All received standardized thoracic epidural and general anesthesia. COMT rs4633 genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Postoperative numerical rating scale (NRS) pain scores and 24-hour rescue analgesia requirements were recorded. Results: The distribution of COMT genotypes was similar between groups ( P = 0.74). Mean NRS scores were lower in Group I compared to Group II at 2 hours (3.6 ± 1.1 vs 4.0 ± 1.2), 6 hours (3.1 ± 1.0 vs 3.5 ± 1.1), 12 hours (2.7 ± 0.9 vs 3.0 ± 1.0), and 24 hours (2.5 ± 0.9 vs 2.8 ± 1.0), with no statistically significant difference ( P > 0.05). At 24 hours, CT genotype patients showed higher pain scores than CC and TT genotypes in both groups (Group I: 2.9 ± 1.0; Group II: 3.1 ± 1.1). Rescue analgesia was required in 30% of Group I and 45% of Group II patients. Time to first rescue analgesia was longer in Group I (8.6 ± 3.2 h vs 7.4 ± 3.1 h), with fewer rescue doses [median 0 (IQR 0–1) vs 1 (IQR 0–2)]. Conclusion: Despite non-significant results, CT genotype showed higher pain and analgesic needs, while pregabalin demonstrated a clinically favorable trend over naproxen.