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The Effect of Analgesic Agents on the Healing Rat Medial Collateral Ligament

From the Department of Orthopaedic Surgery, University of North Carolina, Chapel Hill, North Carolina

^* Address correspondence to Laurence E. Dahners, MD, Bioinformatics Building, CB #7055, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7055 (e-mail: led{at}med.unc.edu).

Background: Studies have suggested that some nonselective nonsteroidal anti-inflammatory drugs, including piroxicam, may improve ligament healing, whereas other nonsteroidal anti-inflammatory drugs, including ibuprofen and the cyclooxygenase-2 inhibitor celecoxib, may have no effect on the mechanical properties or may even deter the healing process. These results might reflect variations in cyclooxygenase enzyme selectivity by different drugs or, alternatively, may be related to their analgesic properties because it is generally accepted that early activity improves ligament healing.

Hypothesis: Nonselective nonsteroidal anti-inflammatory drugs improve ligament healing, whereas other analgesics provide lesser degrees of improvement, and cyclooxygenase-2 inhibitors are detrimental.

Study Design: Controlled laboratory study.

Methods: One hundred fifty-five Sprague-Dawley rats were divided into 7 treatment groups (piroxicam, naproxen, rofecoxib, butorphanol, 2 doses of acetaminophen, and control). The right medial collateral ligament of each rat was transected, and the drugs were administered postoperatively on days 1 to 6. On day 14, the rats were sacrificed, and mechanical testing was performed on the medial collateral ligament.

Results: The piroxicam group demonstrated significantly greater load to failure (27%) compared with the control. No significant differences were observed between other groups.

Conclusions: Piroxicam improves ligament healing, but this effect cannot be attributed to all nonselective nonsteroidal anti-inflammatory drugs. Opiate analgesics, acetaminophen, and cyclooxygenase-2 inhibitors do not appear to categorically affect ligament healing.

Clinical Relevance: In the treatment of ligament injury, piroxicam may be a drug of choice.

Key Words: acetaminophen • analgesic • ligament • piroxicam • cyclooxygenase (COX)

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