Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
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Effects of Medetomidine on Analgesia and Sedation in Rats

Medetomidine의 투여가 흰쥐의 진통과 진정효과에 미치는 영향

  • Jang, Hwan-Soo (Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute Kyungpook National University) ;
  • Lee, Maan-Gee (Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute Kyungpook National University)
  • 장환수 (경북대학교 의과대학 약리학교실, 경북대학교 뇌과학연구소) ;
  • 이만기 (경북대학교 의과대학 약리학교실, 경북대학교 뇌과학연구소)
  • Accepted : 2010.10.04
  • Published : 2010.12.31
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Abstract

The effects of medetomidine on the degree of analgesia and sedation in rats were evaluated. The rats were randomly divided into six groups: saline, 1 mL/kg (group 'Saline'); butorphanol, 2.0 mg/kg; medetomidine, 0.2, 0.4, 0.8 or 1.6 mg/kg (group 'MED0.2', 'MED0.4', 'MED0.8' and 'MED1.6', respectively). The degree of analgesia was measured in the $50^{\circ}C$ hot-water tail-flick latency test, and the degree of sedation was evaluated using the numerical sedation score (NSS) and the righting reflex. All doses of medetomidine, except MED0.2, significantly increased the analgesic effect compared to the Saline group. Variables in the MED0.4 and MED0.8 groups, but not in the MED1.6 group, were significantly increased compared to those in the MED0.2 group. However, analgesia with all doses of medetomidine was not significantly different compared to that with butorphanol. Saline and butorphanol treatments did not induce sedation and loss of righting reflex during the recording period. NSS in the MED0.4, MED0.8 and MED1.6 groups were significantly higher than that in the MED0.2 group. NSS in the MED0.8 and MED1.6 groups were not significantly different from that in the MED0.4 group. The latency to loss of righting reflex in the MED0.8 and MED1.6 groups decreased significantly compared to that in the MED0.2 group. Thus, 0.4 and 0.8 mg/kg of medetomidine provided not only reliable analgesia but also sedation to rats. In conclusion, 0.4 to 0.8 mg/kg medetomidine could be a useful chemical restraint method in rats.

Medetomdine의 투여가 흰쥐의 진통과 진정효과에 미치는 영향에 대하여 평가하였다. 실험동물은 생리식염수 1 ml/kg 투여군 (group 'Saline'), butorphanol, 2.0 mg/kg 투여군 (group 'BUT'), medetomidine, 0.2, 0.4, 0.8 or 1.6 mg/kg 투여군 (각각 group 'MED0.2', 'MED0.4', 'MED0.8' and 'MED1.6') 등 6개의 실험군으로 나누어졌다. 진통효과는 $50^{\circ}C$ hot-water tail-flick latency test로 측정하였고, 진정효과는 numerical sedation score (NSS)와 정위반사 (righting reflex)로 평가하였다. MED0.2군을 제외한 모든 medetomidine 투여군들이 Saline군에 비해 유의적인 진통효과의 증가를 보였다. MED0.2군과 비교할 때 MED0.4와 MED0.8군은 유의적인 진통효과의 상승을 보였으나, MED1.6군은 유의적인 변화를 보이지 않았다. BUT군과 모든 medetomidine 투여군은 진통효과에서 유의적인 차이를 보이지 않았다. Saline과 butorphanol의 투여는 진정효과와 정위반사의 소실을 유발하지 않았다. Medetomidine의 투여 용량의 증가는 진정효과를 증가시켰다. MED0.2군과 비교할 때 MED0.4, MED0.8과 MED1.6군의 NSS가 유의적으로 증가하였으나, MED0.4군에 비해서는 MED0.8과 MED1.6군이 유의적인 차이를 나타내지 않았다. 정위반사의 소실 시간은 MED0.2군에 비해 MED0.8과 MED1.6군이 유의적으로 감소하였다. 본 실험의 결과로 볼 때, 흰쥐에서 medetomidine 0.4에서 0.8 mg/kg 이내의 용량을 복강내 투여할 때 신뢰할 수 있는 진통효과와 진정효과를 동시에 얻을 수 있으며, 따라서 흰쥐의 진정, 진통 및 화학적 보정 목적에 적절한 용량임을 알 수 있었다.

Keywords

References

  1. Asano T, Dohi S, Ohta S, Shimonaka H, Iida H. Antinociception by epidural and systemic alpha(2)-adrenoceptor agonists and their binding affinity in rat spinal cord and brain. Anesth Analg 2000; 90: 400-407.
  2. Back SK, Won SY, Hong SK, Na HS. Gabapentin relieves mechanical, warm and cold allodynia in a rat model of peripheral neuropathy. Neurosci Lett 2004; 368: 341-344. https://doi.org/10.1016/j.neulet.2004.07.091
  3. Bol CJ, Vogelaar JP, Mandema JW. Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats. J Pharmacol Exp Ther 1999; 291: 153-160.
  4. Buerkle H, Yaksh TL. Pharmacological evidence for different alpha 2-adrenergic receptor sites mediating analgesia and sedation in the rat. Br J Anaesth 1998; 81: 208-215. https://doi.org/10.1093/bja/81.2.208
  5. Eisenach JC, Dewan DM. Intrathecal clonidine in obstetrics: sheep studies. Anesthesiology 1990; 72: 663-668. https://doi.org/10.1097/00000542-199004000-00015
  6. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 1991; 14: 219-245. https://doi.org/10.1146/annurev.ne.14.030191.001251
  7. Filos KS, Goudas LC, Patroni O, Polyzou V. Intrathecal clonidine as a sole analgesic for pain relief after cesarean section. Anesthesiology 1992; 77: 267-274. https://doi.org/10.1097/00000542-199208000-00008
  8. Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 1996; 84: 873-881. https://doi.org/10.1097/00000542-199604000-00015
  9. Heinricher MM, McGaraughty S, Farr DA. The role of excitatory amino acid transmission within the rostral ventromedial medulla in the antinociceptive actions of systemically administered morphine. Pain 1999; 81: 57-65. https://doi.org/10.1016/S0304-3959(98)00271-1
  10. Howe JR, Yaksh TL, Go VL. The effect of unilateral dorsal root ganglionectomies or ventral rhizotomies on alpha 2-adrenoceptor binding to, and the substance P, enkephalin, and neurotensin content of, the cat lumbar spinal cord. Neuroscience 1987; 21: 385-394. https://doi.org/10.1016/0306-4522(87)90129-1
  11. Jang HS, Choi HS, Lee SH, Jang KH, Lee MG. Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole. Vet Anaesth Analg 2009;
  12. Jang HS, Kwon YS, Lee MG, Jang KH. The effect of tiletamine/zolazepam (Zoletile) combination with xylazine or medetomidine on electroencephalograms in dogs. J Vet Med Sci 2004; 66: 501-507. https://doi.org/10.1292/jvms.66.501
  13. Jang HS, Lee MG. Atipamezole changes the antinociceptive effects of butorphanol after medetomidine-ketamine anaesthesia in rats. Vet Anaesth Analg 2009; 36: 591-596. https://doi.org/10.1111/j.1467-2995.2009.00497.x
  14. Kanda T, Hikasa Y. Effects of medetomidine and midazolam alone or in combination on the metabolic and neurohormonal responses in healthy cats. Can J Vet Res 2008; 72: 332-339.
  15. Malavasi LM, Nyman G, Augustsson H, Jacobson M, Jensen-Waern M. Effects of epidural morphine and transdermal fentanyl analgesia on physiology and behaviour after abdominal surgery in pigs. Lab Anim 2006; 40: 16-27. https://doi.org/10.1258/002367706775404453
  16. Meng XW, Budra B, Skinner K, Ohara PT, Fields HL. Noradrenergic input to nociceptive modulatory neurons in the rat rostral ventromedial medulla. J Comp Neurol 1997; 377: 381-391. https://doi.org/10.1002/(SICI)1096-9861(19970120)377:3<381::AID-CNE6>3.0.CO;2-Z
  17. Meyer RE, Fish RE: Pharmacology of injectable anesthetics, sedatives, and tranquilizers. In: Anesthesia and analgesia in laboratory animals, 2nd ed. Edited by R. Fish, P. Danneman, M. Brown, A. Karas. San Diego: Academic Press, pp. 50-54, 2008
  18. Millan MJ. Descending control of pain. Prog Neurobiol 2002; 66: 355-474. https://doi.org/10.1016/S0301-0082(02)00009-6
  19. Morgan D, Cook CD, Smith MA, Picker MJ. An examination of the interactions between the antinociceptive effects of morphine and various mu-opioids: the role of intrinsic efficacy and stimulus intensity. Anesth Analg 1999; 88: 407-413.
  20. Norman JC, Narfstrom K, Barrett PM. The effects of medetomidine hydrochloride on the electroretinogram of normal dogs. Vet Ophthalmol 2008; 11: 299-305. https://doi.org/10.1111/j.1463-5224.2008.00650.x
  21. Park JH, Kim SK, Kim HN, Sun B, Koo S, Choi SM, Bae H, Min BI. Spinal cholinergic mechanism of the relieving effects of electroacupuncture on cold and warm allodynia in a rat model of neuropathic pain. J Physiol Sci 2009; 59: 291-298. https://doi.org/10.1007/s12576-009-0035-9
  22. Slingsby LS, Murrell JC, Taylor PM. Combination of dexmedetomidine with buprenorphine enhances the antinociceptive effect to a thermal stimulus in the cat compared with either agent alone. Vet Anaesth Analg 37: 162-170.
  23. Slingsby LS, Taylor PM. Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study. J Vet Pharmacol Ther 2008; 31: 135-142. https://doi.org/10.1111/j.1365-2885.2007.00931.x
  24. Yaksh TL. Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav 1985; 22: 845-858. https://doi.org/10.1016/0091-3057(85)90537-4
  25. Young SS, Schilling AM, Skeans S, Ritacco G. Short duration anaesthesia with medetomidine and ketamine in cynomolgus monkeys. Lab Anim 1999; 33: 162-168. https://doi.org/10.1258/002367799780578363
  26. Zhang WS, Xu H, Xu B, Sun S, Deng XM, Zhang YQ. Antihyperalgesic effect of systemic dexmedetomidine and gabapentin in a rat model of monoarthritis. Brain Res 2009; 1264: 57-66. https://doi.org/10.1016/j.brainres.2009.01.029