AQUATIC ANIMALS 1356 Scientific Reports: Original Study JAVMA, Vol 230, No. 9, May 1, 2007 A nalgesic drug administration under conditions con- sidered painful in humans is regarded as the stan- dard of veterinary practice for all vertebrate species. 1,2 In mammals, peri- and postoperative management of pain facilitate recovery and healing, reduce morbidity and death, and contribute to rapid return to normal ac- tivities. 3,4 With respect to analgesic drugs, relevant data for reptiles are lacking even though reptiles are com- monly maintained as companion animals and heavily represented in zoologic and scientific laboratory col- lections. Thus, there is a fundamental need for studies evaluating species-relevant nociceptive behaviors and analgesic drug efficacy and pharmacodynamics, as well as mechanisms underlying nociception in reptiles. 1,5 Opioids, the most effective drugs for controlling pain in mammals, are classified according to receptor subtypes—µ, κ, and δ. For pain management in mam- mals, many clinicians prefer administering either a Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles Kurt K. Sladky, MS, DVM, DACZM; Vjekoslav Miletic, PhD; Joanne Paul-Murphy, DVM, DACZM; Matthew E. Kinney, BS; Rebecca K. Dallwig, BS; Stephen M. Johnson, MD, PhD From the Departments of Surgical Sciences (Sladky, Paul-Murphy, Kinney, Dallwig) and Comparative Biosciences (Johnson), and the Conservation Health Consortium (Sladky, Paul-Murphy), School of Veterinary Medicine, and the Department of Anesthesiology, School of Medicine and Public Health (Miletic), University of Wisconsin, Madison, WI 53706. Supported by a grant from the Morris Animal Foundation (#D04ZO- 97), Englewood, Colo. The authors thank Robert Creighton for technical assistance. Address correspondence to Dr. Sladky. Objective—To test the hypothesis that butorphanol or morphine induces antinociception with minimal respiratory depression in conscious red-eared slider turtles. Design—Prospective crossover study. Animals—37 adult male and female red-eared slider turtles (Trachemys scripta). Procedures—Antinociception (n = 27 turtles) and respiratory (10 turtles) experiments were performed. Infrared heat stimuli were applied to the plantar surface of turtle limbs. Ther- mal withdrawal latencies were measured before and at intervals after SC administration of physiologic saline (0.9% NaCl) solution, butorphanol tartrate (2.8 or 28 mg/kg [1.27 or 12.7 mg/lb]), or morphine sulfate (1.5 or 6.5 mg/kg [0.68 or 2.95 mg/lb]). Ventilation was assessed in freely swimming turtles before and after SC administration of saline solution, butorphanol (28 mg/kg), or morphine (1.5 mg/kg). Results—For as long as 24 hours after injection of saline solution or either dose of butor- phanol, thermal withdrawal latencies among turtles did not differ. Low- and high-dose mor- phine injections increased latencies significantly by 8 hours. Ventilation was not altered by saline solution administration, was temporarily depressed by 56% to 60% for 1 to 2 hours by butorphanol (28 mg/kg) administration, and was significantly depressed by a maximum of 83 ± 9% at 3 hours after morphine (1.5 mg/kg) injection. Butorphanol and morphine de- pressed ventilation by decreasing breathing frequency. Conclusions and Clinical Relevance—Although widely used in reptile species, butorphanol may not provide adequate antinociception for invasive procedures and caused short-term respiratory depression in red-eared slider turtles. In contrast, morphine apparently provid- ed antinociception but caused long-lasting respiratory depression. (J Am Vet Med Assoc 2007;230:1356–1362) ABBREVIATIONS V · E Ventilation VT Tidal volume µ-opioid receptor agonist (eg, morphine) or a mixed- opioid κ-receptor agonist–µ-receptor antagonist (eg, butorphanol); the latter is favored because of efficacy and relative safety. For postoperative pain control in reptiles, anecdotal reports recommend administration of butorphanol at mammalian-derived dosages. How- ever, to our knowledge, there are no clinical data to substantiate that butorphanol is an effective analgesic drug in reptiles. In contrast, there is minimal evidence that morphine provides antinociception in lizards and crocodiles, 6,7 but there is limited information with re- spect to interspecies differences; dose-dependent ef- fects; duration of drug efficacy; and potentially fatal drug-related adverse effects, such as respiratory depres- sion. In mammals, µ- and δ-opioid receptor activation in the brainstem causes respiratory depression. 8,9 Simi- larly, µ-opioid receptor activation abolishes respiratory motor output in isolated turtle brainstems in vitro. 10 However, little is known about opioid receptor activa- tion and subsequent alteration of breathing in awake reptiles after administration of clinically relevant drugs, such as butorphanol or morphine.