• 1.

    Mosley C. Pain and nociception in reptiles. Vet Clin North Am Exot Anim Pract 2011;14:45 60.

  • 2.

    Holton L, Reid J, Scott EM, et al. Development of a behavior-based scale to measure acute pain in dogs. Vet Rec 2001;148:525 531.

  • 3.

    Reid J, Scott EM, Calvo G, et al. Definitive Glasgow acute pain scale for cats: validation and intervention level. Vet Rec 2017;180:449 452.

  • 4.

    Epstein ME, Rodan I, Griffenhagen G, et al. 2015 AAHA/AAFP pain management guidelines for dogs and cats. J Feline Med Surg 2015;17:251 272.

  • 5.

    Read MR. Evaluation of the use of anesthesia and analgesia in reptiles. J Am Vet Med Assoc 2004;224:547 552.

  • 6.

    Sladky KK, Mans C. Clinical analgesia in reptiles. J Exot Pet Med 2012;21:158 167.

  • 7.

    Sladky KK. Analgesia. In: Mader DR, Divers S, eds. Current therapy in reptile medicine and surgery. 3rd ed. St Louis: Elsevier-Saunders, 2014;217 228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Mosley C. Reptile-specific considerations. In: Gaynor JS, Muir WW, eds. Handbook of veterinary pain management. 3rd ed. St Louis: Elsevier, 2015;42 60.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Sladky KK, Mans C. Analgesia. In: Divers SJ, Stahl SJ, eds. Mader's reptile and amphibian medicine and surgery. St Louis: Elsevier, 2019;465 474.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    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;230:1356 1362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Sladky KK, Kinney ME, Johnson SM. Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes. J Am Vet Med Assoc 2008;233:267 273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    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;70:1072 1078.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Baker BB, Sladky KK, Johnson SM. Evaluation of the analgesic effects of oral and subcutaneous tramadol administration in red-eared slider turtles. J Am Vet Med Assoc 2011;238:220 227.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Kinney ME, Johnson SM, Sladky KK. Behavioral evaluation of red-eared slider turtles (Trachemys scripta elegans) administered either morphine or butorphanol following unilateral gonadectomy. J Herpetol Med Surg 2011;21:54 62.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Leal WP, Carregaro AB, Bressan TF, et al. Antinociceptive efficacy of intramuscular administration of morphine sulfate and butorphanol tartrate in tegus (Salvator merianae). Am J Vet Res 2017;78:1019 1024.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Kharbush RJ, Gutwillig A, Hartzler KE, et al. Antinociceptive and respiratory effects following application of transdermal fentanyl patches and assessment of brain μ-opioid receptor mRNA expression in ball pythons. Am J Vet Res 2017;78:785 795.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Williams CJ, 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;43:429 434.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Bunke LG, Sladky KK, Johnson SM. Antinociceptive efficacy and respiratory effects of dexmedetomidine in ball pythons (Python regius). Am J Vet Res 2018;79:718 726.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Sinclair MD. A review of the physiological effects of α2-agonists related to the clinical use of medetomidine in small animal practice. Can Vet J 2003;44:885 897.

    • Search Google Scholar
    • Export Citation
  • 20.

    Murrell JC, Hellebrekers LJ. Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Vet Anaesth Analg 2005;32:117 127.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Kästner SBR. A2-agonists in sheep: a review. Vet Anaesth Analg 2006;33:79 96.

  • 22.

    Valverde A. Alpha-2 agonists as pain therapy in horses. Vet Clin North Am Equine Pract 2010;26:515 532.

  • 23.

    Sleeman JM, Gaynor J. Sedative and cardiopulmonary effects of medetomidine and reversal with atipamezole in desert tortoises (Gopherus agassizii). J Zoo Wildl Med 2000;31:28 35.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Makau CM, Towett PK, Abelson KS, et al. Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusa subrufa). Brain Behav 2014;4:850 857.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Makau CM, Towett PK, Abelson KS, et al. Modulation of formalin-induced pain-related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii). J Vet Pharmacol Ther 2017;40:439 446.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Bisetto SP, Melo CF, Carregaro AB. Evaluation of sedative and antinociceptive effects of dexmedetomidine, midazolam and dexmedetomidine-midazolam in tegus (Salvator merianae). Vet Anaesth Analg 2018;45:320 328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Giovannoni MP, Ghelardini C, Vergelli C, et al. Alpha 2-agonists as analgesic agents. Med Res Rev 2009;29:339 368.

  • 28.

    Lerche P, Muir WW. Effect of medetomidine on breathing and inspiratory neuromuscular drive in conscious dogs. Am J Vet Res 2004;65:720 724.

  • 29.

    Tamiya J, Ide R, Takahashi M, et al. Effects of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing newborn rats. Paediatr Anaesth 2014;24:1245 1251.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Hilaire G, Viemari JC, Coulon P, et al. Modulation of the respiratory rhythm generator by the pontine noradrenergic A5 and A6 groups in rodents. Respir Physiol Neurobiol 2004;143:187 197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Oliveira LM, Moreira TS, Kuo FS, et al. α1- and α2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats. J Neurophysiol 2016;116:1036 1048.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Tsuzawa K, Minoura Y, Takeda S, et al. Effects of α2-adorenoceptor agonist dexmedetomidine on respiratory rhythm generation of newborn rats. Neurosci Lett 2015;597:117 120.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Fournier S, Kinkead R. Noradrenergic modulation of respiratory motor output during tadpole development: role of α-adrenoreceptors. J Exp Biol 2006;209:3685 3694.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Malte CL, Bundgaard J, Jensen MS, et al. The effects of morphine on gas exchange, ventilation pattern and ventilatory responses to hypercapnia and hypoxia in dwarf caiman (Paleosuchus palpebrosus). Comp Biochem Physiol A Mol Integr Physiol 2018;222:60 65.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Glass ML, Wood SC. Gas exchange and control of breathing in reptiles. Physiol Rev 1983;63:232 260.

  • 36.

    Bickler PE, Buck LT. Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability. Annu Rev Physiol 2007;69:145 170.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Boyer DR. Comparative effects of hypoxia on respiratory and cardiac function in reptiles. Physiol Zool 1966;39:307 316.

  • 38.

    Gratz RK. Ventilatory response of the diamondback water snake, Natrix rhombifera to hypoxia, hypercapnia and increased oxygen demand. J Comp Physiol B 1979;129:105 110.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Wood SC, Hicks JW, Dupré RK. Hypoxic reptiles: blood gases, body temperature and control of breathing. Am Zool 1987;27:21 29.

  • 40.

    Ultsch GR. Ecology and physiology of hibernation and overwintering among freshwater fishes, turtles, and snakes. Biol Rev 1989;64:435 515.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Hicks JW, Wang T. Hypometabolism in reptiles: behavioural and physiological mechanisms that reduce aerobic demands. Respir Physiol Neurobiol 2004;141:261 271.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Jackson DC. Acid-base balance during hypoxic hypometabolism: selected vertebrate strategies. Respir Physiol Neurobiol 2004;141:273 283.

  • 43.

    Yost CS. A new look at the respiratory stimulant doxapram. CNS Drug Rev 2006;12:236 249.

  • 44.

    Heggem B. Doxapram. J Exot Pet Med 2011;20:237 240.

  • 45.

    Skovgaard N, Crossley DA, Wang T. Low cost of pulmonary ventilation in American alligators (Alligator mississippiensis) stimulated with doxapram. J Exp Biol 2016;219:933 936.

    • Search Google Scholar
    • Export Citation
  • 46.

    Martinez-Jimenez D, Hernandez-Divers SJ. Emergency care of reptiles. Vet Clin North Am Exot Anim Pract 2007;10:557 585.

  • 47.

    Smatresk NJ. Chemoreceptor modulation of endogenous respiratory rhythms in vertebrates. Am J Physiol 1990;259:R887 R897.

  • 48.

    Milsom WK, Burleson ML. Peripheral arterial chemoreceptors and the evolution of the carotid body. Respir Physiol Neurobiol 2007;157:4 11.

  • 49.

    Milsom WK. The phylogeny of central chemoreception. Respir Physiol Neurobiol 2010;173:195 200.

  • 50.

    Bartlett D Jr, Tenney SM. Control of breathing in experimental anemia. Respir Physiol 1970;10:384 395.

  • 51.

    Hernandez AB, Kirkness JP, Smith PL, et al. Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse. J Appl Physiol 2012;112:671 680.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52.

    Coote JH. Respiratory and circulatory control during sleep. J Exp Biol 1982;100:223 244.

  • 53.

    Hicks JW, Riedesel ML. Diurnal ventilatory patterns in the garter snake, Thamnophis elegans. J Comp Physiol B 1983;149:503 510.

  • 54.

    Kimmel EC, Whitehead GS, Reboulet JE, et al. Carbon dioxide accumulation during small animal, whole body plethysmography: effects on ventilation, indices of airway function, and aerosol deposition. J Aerosol Med 2002;15:37 49.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55.

    Furilla RA, Coates EL, Bartlett D Jr. The influence of venous CO2 on ventilation in garter snakes. Respir Physiol 1991;83:47 59.

  • 56.

    Nolan WF, Frankel HM. Ventilatory responses to CO2 at different body temperatures in the snake, Coluber constrictor. Experientia 1982;38:943 945.

  • 57.

    Coates EL, Ballam GO. Breathing and upper airway CO2 in reptiles: role of the nasal and vomeronasal systems. Am J Physiol 1989;256:R91 R97.

    • Search Google Scholar
    • Export Citation
  • 58.

    de Andrade DV, Tattersall GJ, Brito SP, et al. The ventilatory response to environmental hypercarbia in the South American rattlesnake, Crotalus durissus. J Comp Physiol B 2004;174:281 291.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59.

    Hargreaves K, Dubner R, Brown F, et al. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988;32:77 88.

  • 60.

    Lim R, Zavou MJ, Milton PL, et al. Measuring respiratory function in mice using unrestrained whole-body plethysmography. J Vis Exp 2014;90:e51755.

    • Search Google Scholar
    • Export Citation
  • 61.

    Gratz RK. Ventilation and gas exchange in the diamondback water snake, Natrix rhombifera. J Comp Physiol B 1978;127:299 305.

  • 62.

    Stinner JN. Ventilation, gas exchange and blood gases in the snake, Pituophis melanoleucus. Respir Physiol 1982;47:279 298.

  • 63.

    Furilla RA, Bartlett D Jr. Intrapulmonary CO2 inhibits inspiration in garter snakes. Respir Physiol 1989;78:207 217.

  • 64.

    Enhorning G, van Schaik S, Lundgren C, et al. Whole-body plethysmography, does it measure tidal volume of small animals? Can J Physiol Pharmacol 1998;76:945 951.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 65.

    Milsom WK, Chatburn J, Zimmer MB. Pontine influences on respiratory control in ectothermic and heterothermic vertebrates. Respir Physiol Neurobiol 2004;143:263 280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 66.

    Bartlett D Jr, Mortola JP, Doll EJ. Respiratory mechanics and control of the ventilatory cycle in the garter snake. Respir Physiol 1986;64:13 27.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67.

    Malte CL, Malte H, Wang T. Episodic ventilation lowers the efficiency of pulmonary CO2 excretion. J Appl Physiol 2013;115:1506 1518.

  • 68.

    Hicks JW, Wood SC. Temperature regulation in lizards: effects of hypoxia. Am J Physiol 1985;248:R595 R600.

  • 69.

    Hicks JW, Wang T. Hypoxic hypometabolism in the anesthetized turtle, Trachemys scripta. Am J Physiol 1999;277:R18 R23.

  • 70.

    Heard DJ. Reptile anesthesia. Vet Clin North Am Exot Anim Pract 2001;4:83 117.

  • 71.

    Mosley CAE. Anesthesia and analgesia in reptiles. Semin Avian Exot Pet Med 2005;14:243 262.

  • 72.

    Smith DA, Barker IK, Allen OB. The effect of ambient temperature and type of wound on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis). Can J Vet Res 1988;52:120 128.

    • Search Google Scholar
    • Export Citation
  • 73.

    Nielsen B. On the regulation of the respiration in reptiles: the effect of temperature and CO2 on the respiration of lizards (Lacerta). J Exp Biol 1961;38:301 314.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 74.

    Glass M, Johansen K. Control of breathing in Acrochordus javanicus, an aquatic snake. Physiol Zool 1976;49:328 340.

  • 75.

    Gregoretti SM, Pleuvry BJ. Interactions between morphine and doxapram in the rabbit and mouse. Br J Anaesth 1977;49:323 329.

  • 76.

    Haji A, Kimura S, Ohi Y. Reversal of morphine-induced respiratory depression by doxapram in anesthetized rats. Eur J Pharmacol 2016;780:209 215.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 77.

    Golder FJ, Hewitt MM, McLeod JF. Respiratory stimulant drugs in the post-operative setting. Respir Physiol Neurobiol 2013;189:395 402.

  • 78.

    Gupta PK, Dundee JW. Morphine combined with doxapram or naloxone: a study of post-operative pain relief. Anaesthesia 1974;29:33 39.

  • 79.

    Gross PM, Marcus ML, Heistad DD. Regional distribution of cerebral blood flow during exercise in dogs. J Appl Physiol 1980;48:213 217.

  • 80.

    Miletich DJ, Ivankovich AD, Albrecht RF, et al. The effects of doxapram on cerebral blood flow and peripheral hemodynamics in the anesthetized and unanesthetized goat. Anesth Analg 1976;55:279 285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 81.

    Brückner JB, Hess W, Schneider E, et al. Doxapram-induced changes in circulation and myocardial efficiency [in German]. Anaesthesist 1977;26:156 164.

    • Search Google Scholar
    • Export Citation

Advertisement

Respiratory and antinociceptive effects of dexmedetomidine and doxapram in ball pythons (Python regius)

Alyssa A. Karklus MS, DVM1, Kurt K. Sladky MS, DVM2, and Stephen M. Johnson MD, PhD1
View More View Less
  • 1 Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706.
  • | 2 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706.

Abstract

OBJECTIVE

To determine the effects of dexmedetomidine, doxapram, and dexmedetomidine plus doxapram on ventilation (e), breath frequency, and tidal volume (Vt) in ball pythons (Python regius) and of doxapram on the thermal antinociceptive efficacy of dexmedetomidine.

ANIMALS

14 ball pythons.

PROCEDURES

Respiratory effects of dexmedetomidine and doxapram were assessed with whole-body, closed-chamber plethysmography, which allowed for estimates of e and Vt. In the first experiment of this study with a complete crossover design, snakes were injected, SC, with saline (0.9% NaCl) solution, dexmedetomidine (0.1 mg/kg), doxapram (10 mg/kg), or dexmedetomidine and doxapram, and breath frequency, e, and Vt were measured before and every 30 minutes thereafter, through 240 minutes. In the second experiment, antinociceptive efficacy of saline solution, dexmedetomidine, and dexmedetomidine plus doxapram was assessed by measuring thermal withdrawal latencies before and 60 minutes after SC injection.

RESULTS

Dexmedetomidine significantly decreased breath frequency and increased Vt but did not affect e at all time points, compared with baseline. Doxapram significantly increased e, breath frequency, and Vt at 60 minutes after injection, compared with saline solution. The combination of dexmedetomidine and doxapram, compared with dexmedetomidine alone, significantly increased e at 30 and 60 minutes after injection and did not affect breath frequency and Vt at all time points. Thermal withdrawal latencies significantly increased when snakes received dexmedetomidine or dexmedetomidine plus doxapram, versus saline solution.

CONCLUSIONS AND CLINICAL RELEVANCE

Concurrent administration of doxapram may mitigate the dexmedetomidine-induced reduction of breathing frequency without disrupting thermal antinociceptive efficacy in ball pythons.

Contributor Notes

Address correspondence to Dr. Johnson (stephen.m.johnson@wisc.edu).

Dr. Karklus' present address is Brook-Falls Veterinary Hospital and Exotic Care Inc, Menomonee Falls, WI 53051.