Abstract
Tramadol (Ultram®, PCCA, Houston, TX) is a non-controlled opioid drug with a dual mechanism of action as a µ-opioid agonist and serotonin/norepinephrine reuptake inhibitor, both of which contribute to analgesia in mammals.1-4,6,7 Respiratory depression is less severe with tramadol compared to morphine in dogs and cats.5,9 Based on these findings, we hypothesized that tramadol would also produce analgesia in reptiles with less respiratory depression than morphine. Thus, we studied the dose- and time-dependent changes in analgesia and respiration caused by tramadol in red-eared slider turtles.
Using a crossover design, oral tramadol (1, 5, 10, and 25 mg/kg), injectable tramadol (10 and 25 mg/kg), and controls were administered to adult, red-eared slider turtles. Analgesia was measured with hindlimb withdrawal latencies to noxious thermal stimuli at 0, 3, 6, 12, 24, 48, 72, and 96 hours post-drug administration. Respiration was measured in freely swimming turtles in individual tanks with access to a small breathing hole. Tramadol (10 mg/kg PO) increased thermal withdrawal latencies for 6–96 hours post-drug compared to controls. In contrast, tramadol (10 mg/kg SC) only increased latencies between 12–48 hours post-drug. Tramadol (25 mg/kg PO or SC) increased latencies for 6–96 hours post-drug, but this dosage was associated with mouth gaping and flaccid limbs and necks. Respiratory depression was observed in all turtles given tramadol (5, 10, 25 mg/kg PO), but, unlike morphine,8 breathing continued at all dosages. Thus, tramadol (10 mg/kg PO) is an effective, long-lasting analgesic drug that may be safer than morphine.
Acknowledgments
This work was supported by the National Institutes of Health [T32 RR17503-01A1 (BBC)] and the National Science Foundation (IOB 0517302).
Literature Cited
1. Collart L, Luthy C, Favario-Constantin C, Dayer P. Duality of the analgesic effect of tramadol in humans. Schweiz Med Wschr. 1993;123(47):2241–2243.
2. Desmueles JA, Piguet V, Collart L, Dayer P. Contribution of monoaminergic modulation to the analgesic effect of tramadol. Brit J Clin Pharmacol. 1996;41(1):7–12.
3. Garrido MJ, Valle M, Campanero MA, Calvo R, Troconiz IF. Modeling of the in vivo antinociceptive interaction between an opioid agonist, (+)-O-Desmethyltramadol, and a monoamine reuptake inhibitor, (-)-O-Desmethyltramadol, in rats. J Pharmacol Exp Ther. 2000;295:352–359.
4. Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K. Mu opioid receptor-dependent and independent components in effects of tramadol. Neuropharmacology. 2006;51:651–658.
5. Mastrocinque S, Fantoni DT. A comparison of pre-operative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. Vet Anaesth Analg. 2003;30:220–228.
6. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther. 1991;260(1):275–285.
7. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL, et al. Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther. 1993;267(1):331–340.
8. Sladky KK, Miletic V, Paul-Murphy J, Kinney ME, Dallwig RK, Johnson SM. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. J Am Vet Med Assoc. 2007;230:1356–1362.
9. Teppema LJ, Nieuwenhuijs D, Olievier CN, Dahan A. Respiratory depression by tramadol in the cat: involvement of opioid receptors. Anesthesiology. 2003;98:420–427.