Antinociceptive efficacy of intramuscular administration of morphine sulfate and butorphanol tartrate in tegus (Salvator merianae)

William P. Leal Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo 13635-900, Brazil.

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Adriano B. Carregaro Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo 13635-900, Brazil.

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Thais F. Bressan Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo 13635-900, Brazil.

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Shayne P. Bisetto Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo 13635-900, Brazil.

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Cristiano F. Melo Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo 13635-900, Brazil.

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Kurt K. Sladky Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53705.

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Abstract

OBJECTIVE To evaluate the antinociceptive efficacy of IM morphine sulfate or butorphanol tartrate administration in tegus (Salvator merianae).

ANIMALS 6 healthy juvenile (12- to 24-month-old) tegus (mean ± SD body weight, 1,484 ± 473 g).

PROCEDURES In a crossover study design, tegus were randomly assigned to treatment order, with a minimum washout period of 15 days between treatments. Each of 5 treatments was administered IM in a forelimb: saline (0.9% NaCl) solution (0.5 mL), morphine sulfate (5 or 10 mg/kg), or butorphanol tartrate (5 or 10 mg/kg). A withdrawal latency test was used to evaluate antinociception, with a noxious thermal stimulus applied to the plantar surface of the hind limb before (0 hours; baseline) and 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after each treatment. Observers were unaware of treatment received.

RESULTS With saline solution, mean hind limb withdrawal latencies (interval to limb withdrawal from the thermal stimulus) remained constant, except at 12 hours. Tegus had higher than baseline mean withdrawal latencies between 0.5 and 1 hour and at 12 hours with morphine at 5 mg/kg and between 1 and 12 hours with morphine at 10 mg/kg. With butorphanol at 5 and 10 mg/kg, tegus maintained withdrawal responses similar to baseline at all assessment points.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that morphine, but not butorphanol, provided antinociception at 5 and 10 mg/kg in tegus as measured by thermal noxious stimulus testing. These data supported the hypothesis that μ-opioid (but not κ-opioid) receptor agonists provide antinociception in reptiles.

Abstract

OBJECTIVE To evaluate the antinociceptive efficacy of IM morphine sulfate or butorphanol tartrate administration in tegus (Salvator merianae).

ANIMALS 6 healthy juvenile (12- to 24-month-old) tegus (mean ± SD body weight, 1,484 ± 473 g).

PROCEDURES In a crossover study design, tegus were randomly assigned to treatment order, with a minimum washout period of 15 days between treatments. Each of 5 treatments was administered IM in a forelimb: saline (0.9% NaCl) solution (0.5 mL), morphine sulfate (5 or 10 mg/kg), or butorphanol tartrate (5 or 10 mg/kg). A withdrawal latency test was used to evaluate antinociception, with a noxious thermal stimulus applied to the plantar surface of the hind limb before (0 hours; baseline) and 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after each treatment. Observers were unaware of treatment received.

RESULTS With saline solution, mean hind limb withdrawal latencies (interval to limb withdrawal from the thermal stimulus) remained constant, except at 12 hours. Tegus had higher than baseline mean withdrawal latencies between 0.5 and 1 hour and at 12 hours with morphine at 5 mg/kg and between 1 and 12 hours with morphine at 10 mg/kg. With butorphanol at 5 and 10 mg/kg, tegus maintained withdrawal responses similar to baseline at all assessment points.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that morphine, but not butorphanol, provided antinociception at 5 and 10 mg/kg in tegus as measured by thermal noxious stimulus testing. These data supported the hypothesis that μ-opioid (but not κ-opioid) receptor agonists provide antinociception in reptiles.

Contributor Notes

Address correspondence to Dr. Carregaro (carregaro@usp.br).
  • 1. Liang YF, Terashima S, Zhu AQ. Distinct morphological characteristics of touch, temperature, and mechanical nociceptive neurons in the crotaline trigeminal ganglia. J Comp Neurol 1995;360:621633.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. ten Donkelaar HJ, de Boer-van Huizen R. A possible pain control system in a non-mammalian vertebrate (a lizard, Gekko gecko). Neurosci Lett 1987;83:6570.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Xia Y, Haddad GG. Major difference in the expression of delta and mu-opioid receptors between turtle and rat brain. J Comp Neurol 2001;436:202210.

  • 4. Sladky KK, Miletic V, Paul-Murphy J, et al. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. J Am Vet Med Assoc 2007;230:13561362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Sladky KK, Kinney ME, Johnson SM. Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes. J Am Vet Med Assoc 2008;233:267273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Wambugu SN, Towett PK, Kiama SG, et al. Effects of opioids in the formalin test in the Speke's hinged tortoise (Kinixys spekii). J Vet Pharmacol Ther 2010;33:347351.

    • Search Google Scholar
    • Export Citation
  • 7. Dahlin J, Kanui TI, Wambugu SN, et al. The suspended formalin test: a method designed for studying formalin-induced behaviour in the Speke's hingeback tortoise (Kinixys spekii). Scand J Lab Anim Sci 2012;39:1115.

    • Search Google Scholar
    • Export Citation
  • 8. Williams CJA, James LE, Bertelsen MF, et al. Tachycardia in response to remote capsaicin injection as a model for nociception in the ball python (Python regius). Vet Anaesth Analg 2016; 43;429434.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Kanui TI, Hole K, Miaron JO. Nociception in crocodiles—capsaicin instillation, formalin and hot plate test. Zoolog Sci 1990;7:537540.

    • Search Google Scholar
    • Export Citation
  • 10. Mans C, Lahner LL, Baker BB, et al. Antinociceptive efficacy of buprenorphine and hydromorphone in red-eared slider turtles (Trachemys scripta elegans). J Zoo Wildl Med 2012;43:662665.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Sladky KK, Kinney ME, Johnson SM. Effects of opioid receptor activation on thermal antinociception in red-eared slider turtles (Trachemys scripta). Am J Vet Res 2009;70:10721078.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Fleming GJ, Robertson SA. Assessments of thermal antinociceptive effects of butorphanol and human observer effect on quantitative evaluation of analgesia in green iguanas (Iguana iguana). Am J Vet Res 2012;73:15071511.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Hargreaves K, Dubner R, Brown F, et al. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988;32:7788.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Sladky KK, Mans C. Clinical analgesia in reptiles. J Exot Pet Med 2012;21:158167.

  • 15. Read MR. Evaluation of the use of anesthesia and analgesia in reptiles. J Am Vet Med Assoc 2004;224:547552.

  • 16. Schnellbacher R. Butorphanol J Exot Pet Med 2010;19:192195.

  • 17. Klein W, Abe AS, Andrade DV, et al. Structure of the posthepatic septum and its influence on visceral topology in the tegu lizard Tupinambis merianae (Teiidae: Reptilia). J Morphol 2003;258:151157.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Andrade DV, Brito SP, Toledo LF, et al. Seasonal changes in blood oxygen transport and acid-base status in the tegu lizard, Tupinambis merianae. Respir Physiol Neurobiol 2004;140:197208.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Skovgaard N, Galli G, Abe A, et al. The role of nitric oxide in regulation of the cardiovascular system in reptiles. Comp Biochem Physiol A Mol Integr Physiol 2005;142:205214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Tattersall GJ, Leite CAC, Sanders CE, et al. Seasonal reproductive endothermy in tegu lizards. Sci Adv 2016;2:e1500951.

  • 21. Diethelm G, Stein G. Hematologic and blood chemistry values in reptiles. In: Mader DR, ed. Reptile medicine and surgery. 2nd ed. Philadelphia: Saunders Elsevier, 2005; 11031118.

    • Search Google Scholar
    • Export Citation
  • 22. Mosley C. Pain and nociception in reptiles. Vet Clin North Am Exot Anim Pract 2011;14:4560.

  • 23. Sladky KK, Mans C. Clinical anesthesia in reptiles. J Exot Pet Med 2012;21:1731.

  • 24. Andrade DV, Sanders C, Milsom WK, et al. Overwintering in tegu lizards. In: Barnes BM, Carey HV, eds. Life in the cold: evolution, mechanisms, adaptation, and application. Fairbanks, Alaska: Institute of Arctic Biology, University of Alaska, 2004; 339348.

    • Search Google Scholar
    • Export Citation

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