The Effects of Morphine on Human Articular Cartilage of the Knee: An In Vitro Study John W. Jaureguito, M.D., Joseph F. Wilcox, M.D., Ronald A. Thisted, Ph.D., Craig Phillips, M.D., Benjamin Cunningham, M.D., and Bruce Reider, M.D. Purpose: The purpose of this study was to determine the metabolic, histologic, and ultrastructural effects of morphine and its combination with saline and bupivacaine on human articular cartilage. Type of Study: In vitro study. Methods: Nonfibrillated human articular cartilage was harvested and transferred into an experimental culture consisting of a control medium, saline, or a combination of morphine/saline or morphine/saline/bupivacaine for 12, 24, or 72 hours. Each sample was radiola- beled to assess proteoglycan synthesis. Histologic and ultrastructural effects were also examined. Results: We found a significant, dose-related, transient decrease in 35 SO 4 incorporation in the morphine/saline samples at 12 hours, and in the saline only samples at 24 hours. We found no evidence of histologic or ultrastructural damage to the cartilage. Conclusions: Morphine and saline can both produce a transient decrease in 35 SO 4 incorporation that normalizes by 72 hours. This study does not suggest any contraindication to the use of intra-articular morphine as a postoperative analgesic. Key Words: Morphine—Bupivacaine—Cartilage—Analgesia—Arthroscopy. O pioid analgesics have traditionally been associ- ated with actions on the central nervous system. However, animal studies have shown that exogenous opioid agonists have peripheral antinociceptive effects in inflamed tissue in rats. 1 A study of patients under- going arthroscopic knee surgery showed that a low dose of intra-articular morphine produced more pro- nounced postoperative analgesia than the same dose given intravenously. Pain scores were significantly lower at 3, 4, and 6 hours postoperatively, and the need for supplemental analgesic agents was also sig- nificantly lower. Interestingly, we found no major side effects after the intra-articular administration of 1 mg of morphine. 2 This is noteworthy because the occur- rence of side effects limits systemic and spinal admin- istration of morphine. Joshi et al. 3 corroborated these findings in a ran- domized, double-blind, prospective study. In that study, the morphine group had a significantly lower visual analog pain score and required less systemic analgesics than the saline control group. In addition, plasma assayed for morphine and its metabolites in- dicated levels too low to produce effective analgesia. The authors concluded that this evidence suggests that analgesia was mediated by local action within the joint. A number of studies 3-7 have shown that intra-artic- ular morphine will provide prolonged analgesia for 24 hours or longer compared with saline or bupivacaine. This is advantageous because arthroscopy is routinely performed on an outpatient basis. We have shown that, when used as a postoperative analgesic following outpatient knee surgery, intra-articular morphine low- ers visual analog pain scale scores at 24 hours. Pa- From the East Bay Sports Medicine & Orthopaedic Specialists, Fremont, California (J.J.); the Department of Orthopaedic Surgery at Emory University, Atlanta, Georgia (J.W.); and the Section of Orthopaedic Surgery and Rehabilitation Medicine, University of Chicago, Chicago, Illinois (R.T., C.P., B.C., B.R.), U.S.A. Supported by the University of Chicago Section of Orthopaedic Surgery and Rehabilitation Medicine. All work was performed in the Section of Orthopaedic Surgery and Rehabilitation Medicine at the University of Chicago, Chi- cago, IL. Address correspondence and reprint requests to Joseph F. Wil- cox, M.D., Northeast Orthopedics, 164 Wetherby Lane, Wester- ville, OH 43081, U.S.A. E-mail: jfwilco@aol.com © 2002 by the Arthroscopy Association of North America 0749-8063/02/1806-2573$35.00/0 doi:10.1053/jars.2002.32587 631 Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 18, No 6 (July-August), 2002: pp 631– 636