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Objective: To compare the analgesic efficacy of a traditional epidurally delivered bupivacaine/fentanyl combination with a repeat bolus intrathecal morphine technique in the management of post-thoracotomy pain and to assess further the effect of cyclooxygenase (COX) inhibition on both modalities., Design: Prospective, randomized, blinded study., Setting: University teaching hospital., Participants: Patients having thoracic surgery., Interventions: Epidural and intrathecal catheters were inserted. Blood and urine samples were collected for analysis. COX-1 and COX-2 inhibition with ibuprofen and nimesulide (COX-2 selective) was instituted., Measurements and Main Results: Pain was assessed at rest and coughing by visual analog scale. Peak expiratory flow rate, patient satisfaction rating, sedation score, analgesic requirements, and preoperative and postoperative urinary creatinine levels were measured. The spinal and nimesulide combination showed the lowest pain scores (p < 0.001), least reduction in peak expiratory flow rate (p < 0.001), and highest patient satisfaction rating (p = 0.02). COX inhibition did not affect analgesic requirements in the epidural group or increase urinary creatinine in any group., Conclusion: The intrathecal morphine and nimesulide combination offered significantly better analgesia than any other combination studied. The efficacious interaction between opioids and nonsteroidal anti-inflammatory drugs may be COX-2 mediated., (Copyright 2002, Elsevier Science (USA). All rights reserved.)