Original ArticlesPreclinical Toxicity Study of Intrathecal Administration of the Pain Relievers Dextrorphan, Dextromethorphan, and Memantine in the Sheep Model
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MATERIALS AND METHODS
After approval by the Institutional Animal Care and Use Committee at The University of Texas M.D. Anderson Cancer Center; this study was conducted at M.D. Anderson Cancer Center-Science Park’s Department of Veterinary Sciences (Bastrop, TX) in strict accordance to the Guide for the Care and Use of Laboratory Animals published by National Research Council (42). The 48, one- and two-year-old Rambouillet/Suffolk-cross sheep used in this study weighed between 22 and 58 kg. The male sheep (N = 39)
RESULTS
All 48 sheep randomly received continuous intrathecal administration of dextrorphan, dextromethorphan, or memantine via subcutaneous, programmable continuous-infusion pumps (Medtronic Synchromed, pump models 8615 and 8617). Of these 48 animals, 41 were actually used in the study groups. Of the seven animals excluded from the study, three animals had questionable patency of the intrathecal catheters; one animal had a neurologic deficit caused by intraoperative trauma; another animal developed a
DISCUSSION
The administration of intrathecal or epidural morphine for chronic pain states is widespread and well-established (15,18). However, unpredicted side effects such as ventilatory depression, itching, and urinary retention have been reported (16) and the use of spinally administered morphine has been accompanied by reports of tolerance (43). Common clinical practice including our experience and that of others (44) found that morphine tolerance could develop to a point where intrathecal doses of 50
ACKNOWLEDGMENTS
We would like to thank Richard Terrell, Kyle Voelker, Rodney Helgren and Gerald Costello for their valuable assistance in conducting this study. We would also like to thank Medtronic, Inc. (Minneapolis, MN) for the use of the implantable infusion devices. Quanyun Xu, Ph.D. was instrumental in preparing the antagonists.
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