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Electroencephalographic responses of anaesthetised pigs to intraperitoneal injection of sodium pentobarbital

Published online by Cambridge University Press:  01 January 2023

NJ Kells ,
NJ Beausoleil ,
MA Sutherland  and
CB Johnson
NJ Kells*
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
NJ Beausoleil
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
MA Sutherland
Affiliation:
AgResearch Ltd, Ruakura Research Centre, Hamilton 3240, New Zealand
CB Johnson
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
*
∗ Contact for correspondence and requests for reprints: N.J.Kells@massey.ac.nz
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Abstract

Small laboratory animals are commonly euthanased via intraperitoneal (IP) injection of sodium pentobarbital. However, there is concern that animals may experience pain prior to loss of consciousness with this delivery route. The present study investigated electroencephalographic (EEG) nociceptive responses of anaesthetised pigs to IP sodium pentobarbital injection using an established minimal anaesthesia model. Thirty commercial white line entire male pigs aged 10-15 days were minimally anaesthetised with halothane in oxygen. Following 10 min of baseline EEG data collection, pigs had their tails docked using side-cutters and, after a further 5-min interval, were euthanased via IP injection of sodium pentobarbital (250 mg kg-1). The summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were derived from the EEG data. For each variable in each pig, means were calculated for the following 60-s periods: immediately prior to tail-docking (baseline 1); immediately prior to pentobarbital injection (at least 4 min after docking; baseline 2); and for two consecutive 60-s periods immediately following pentobarbital injection (P1 and P2). Statistical analyses revealed no differences between the two baseline periods, indicating that transient EEG changes induced by tail-docking had resolved prior to pentobarbital injection. IP pentobarbital injection induced a significant increase in F50 and decrease in PTOT of the EEG during P1. This response is characteristic of acute nociception, indicating that conscious pigs likely perceive IP sodium pentobarbital as painful in the period prior to loss of consciousness.

Keywords

animal welfareEEGeuthanasianociceptionpentobarbitalpig
Type
Articles
Information
Animal Welfare , Volume 27 , Issue 3 , August 2018 , pp. 205 - 214
Copyright
© 2018 Universities Federation for Animal Welfare

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References

Ambrose, N 1998 Refinement of routine procedures on laboratory rodents. School of Medicine and Dentistry, University of Birmingham, Birmingham, UKGoogle Scholar
Antunes, LM, Golledge, HD, Roughan, JV and Flecknell, PA 2003 Comparison of electroencephalogram activity and auditory evoked responses during isoflurane and halothane anaesthesia in the rat. Veterinary Anaesthesia and Analgesia 30: 15–23. https://doi.org/10.1046/j.1467-2995.2003.00085.xGoogle ScholarPubMed
Arioli, V and Rossi, E 1970 Errors related to different techniques of intraperitoneal injection in mice. Applied Microbiology 19: 704–705CrossRefGoogle ScholarPubMed
Baek, JM, Kwak, SC, Kim, JY, Ahn, SJ, Jun, HY, Yoon, KH, Lee, MS and Oh, J 2015 Evaluation of a novel technique for intraperitoneal injections in mice. Laboratory Animals (NY) 44: 440–444. https://doi.org/10.1038/laban.880CrossRefGoogle ScholarPubMed
Bergamasco, L, Accatino, A, Priano, L, Neiger-Aeschbacher, G, Cizinauskas, S and Jaggy, A 2003 Quantitative electroencephalographic findings in beagles anaes-thetized with propofol. Veterinary Journal 166: 58–66. https://doi.org/10.1016/S1090-0233(02)00254-XGoogle ScholarPubMed
Bromm, B 1984 Pain Measurement in Man: Neurophysiological Correlates of Pain. Elsevier: New York, USAGoogle Scholar
Chen, ACN, Dworkin, SF, Haug, J and Gehrig, J 1989 Topographic brain measures of human pain and pain responsivity. Pain 37: 129–141. https://doi.org/10.1016/0304-3959(89)90125-5CrossRefGoogle ScholarPubMed
Claasen, V 1994 Intraperitoneal drug administration. In: Huston, J (ed) Techniques in the Behavioral and Neural Sciences pp 46–58. Elsevier: New York, USAGoogle Scholar
Devonshire, IM, Greenspon, CM and Hathway, GJ 2015 Developmental alterations in noxious-evoked EEG activity recorded from rat primary somatosensory cortex. Neuroscience 305: 343–350. https://doi.org/10.1016/j.neuroscience.2015.08.004CrossRefGoogle ScholarPubMed
Gibson, TJ, Johnson, CB, Murrell, JC, Hulls, CM, Mitchinson, SL, Stafford, KJ, Johnstone, AC and Mellor, DJ 2009 Electroencephalographic responses of halothane-anaesthetised calves to slaughter by ventral-neck incision without prior stun-ning. New Zealand Veterinary Journal 57: 77–83. https://doi.org/10.1080/00480169.2009.36882Google Scholar
Gibson, TJ, Johnson, CB, Stafford, KJ, Mitchinson, SL and Mellor, DJ 2007 Validation of the acute electroencephalographic responses of calves to noxious stimulus with scoop dehorning. New Zealand Veterinary Journal 55: 152–157. https://doi.org/10.1080/00480169.2007.36760Google ScholarPubMed
Grier, RL and Schaffer, CB 1990 Evaluation of intraperitoneal and intrahepatic administration of a euthanasia agent in animal shelter cats. Journal of the American Veterinary Medical Association 197: 1611–1615Google ScholarPubMed
Haga, H and Ranheim, B 2005 Castration of piglets: the anal-gesic effects of intratesticular and intrafunicular lidocaine injection. Veterinary Anaesthesia and Analgesia 32: 1–9. https://doi.org/10.1111/j.1467-2995.2004.00225.xCrossRefGoogle Scholar
Hudson, RJ, Stanski, DR, Saidman, LJ and Meathe, E 1983 A model for studying depth of anesthesia and acute tolerance to thiopental. Anesthesiology 59: 301–308. https://doi.org/10.1097/00000542-198310000-00006CrossRefGoogle Scholar
Hunt, SP, Pini, A and Evan, G 1987 Induction of c-fos-like pro-tein in spinal cord neurons following sensory stimulation. Nature 328: 632–634. https://doi.org/10.1038/328632a0CrossRefGoogle Scholar
Jinks, SL, Simons, CT, Dessirier, J-M, Carstens, MI, Antognini, JF and Carstens, E 2002 c-fos induction in rat superficial dorsal horn following cutaneous application of noxious chemical or mechanical stimuli. Experimental Brain Research 145:261–269. https://doi.org/10.1007/s00221-002-1128-3CrossRefGoogle ScholarPubMed
Johnson, CB, Stafford, KJ, Sylvester, S, Ward, R, Mitchinson, S and Mellor, DJ 2005a Effects of age on electroencephalograph-ic responses to castration in lambs anaesthetised using halothane in oxygen. New Zealand Veterinary Journal 53: 433–437. https://doi.org/10.1080/00480169.2005.36589CrossRefGoogle Scholar
Johnson, CB, Sylvester, SP, Stafford, KJ, Mitchinson, SL, Ward, RN and Mellor, DJ 2009 Effects of age on the electroen-cephalographic response to castration in lambs anaesthetized with halothane in oxygen from birth to 6 weeks old. Veterinary Anaesthesia and Analgesia 36: 273–279. https://doi.org/10.1111/j.1467-2995.2009.00448.xCrossRefGoogle Scholar
Johnson, CB and Taylor, PM 1997 Effects of alfentanil on the equine electroencephalogram during anaesthesia with halothane in oxygen. Research in Veterinary Science 62: 159–163. https://doi.org/10.1016/S0034-5288(97)90139-9Google ScholarPubMed
Johnson, CB and Taylor, PM 1998 Comparison of the effects of halothane, isoflurane and methoxyflurane on the electroen-cephalogram of the horse. British Journal of Anaesthesia 81: 748–753. https://doi.org/10.1093/bja/81.5.748CrossRefGoogle Scholar
Johnson, CB, Wilson, P, Woodbury, M and Caulkett, N 2005b Comparison of analgesic techniques for antler removal in halothane-anaesthetised red deer (Cervus elaphus): electroen-cephalographic responses. Veterinary Anaesthesia and Analgesia 32:61–71. https://doi.org/10.1111/j.1467-2995.2005.00228.xCrossRefGoogle Scholar
Johnson, CB, Young, SS and Taylor, PM 1994 Analysis of the frequency spectrum of the equine electroencephalogram during halothane anaesthesia. Research in Veterinary Science 56: 373–378. https://doi.org/10.1016/0034-5288(94)90155-4CrossRefGoogle ScholarPubMed
Kells, NJ, Beausoleil, NJ, Sutherland, MA, Morrison, RB and Johnson, CB 2017a Electroencephalographic responses of anaes-thetised pigs (Sus scrofa) to tail docking using clippers or cautery iron, performed at two or twenty days of age. Veterinary Anaesthesia & Analgesia 44: 1156–1165. https://doi.org/10.1016/j.vaa.2017.02.003CrossRefGoogle Scholar
Kells, NJ, Beausoleil, NJ, Sutherland, MA, Morrison, RB and Johnson, CB 2017b Electroencephalographic assessment of oral meloxicam, topical anaesthetic cream and cautery iron for miti-gating acute pain in pigs (Sus scrofa) undergoing tail docking. Veterinary Anaesthesia & Analgesia 44: 1166–1174. https://doi.org/10.1016/j.vaa.2017.02.004CrossRefGoogle Scholar
Kongara, K, Chambers, JP and Johnson, CB 2010 Electroencephalographic responses of tramadol, parecoxib and morphine to acute noxious electrical stimulation in anaesthetised dogs. Research in Veterinary Science 88: 127–133. https://doi.org/10.1016/j.rvsc.2009.05.012CrossRefGoogle ScholarPubMed
Kongara, K, Johnson, L, Kells, N, Johnson, C, Dukkipati, V and Mitchinson, SL 2014 Alteration of electroencephalographic responses to castration in cats by administration of opioids. GSTF Journal of Veterinary Science 1: 38–42. https://doi.org/10.5176/2345-7880_1.1.5CrossRefGoogle Scholar
Leary, S, Underwood, W, Anthony, R, Cartner, S, Corey, D, Grandin, T, Greenacre, CB, Gwaltney-Bran, S, McCrackin, MA and Meyer, R 2013 AVMA Guidelines for the Euthanasia of Animals. AVMA: London, UKGoogle Scholar
Martin-Cancho, MF, Lima, JR, Luis, L, Crisostomo, V, Ezquerra, LJ, Carrasco, MS and Uson-Gargallo, J 2003 Bispectral index, spectral edge frequency 95%, and median fre-quency recorded for various concentrations of isoflurane and sevoflurane in pigs. American Journal of Veterinary Research 64: 866–873. https://doi.org/10.2460/ajvr.2003.64.866Google Scholar
Mellor, D, Cook, C and Stafford, K 2000 Quantifying some responses to pain as a stressor. In: Moberg, G and Mench, J (eds) The Biology of Animal Stress pp 171–198. CABI Publishing: Wallingford, UK. https://doi.org/10.1079/9780851993591.0171CrossRefGoogle Scholar
Miner, NA, Koehler, J and Greenaway, L 1969 Intraperitoneal injection of mice. Applied Microbiology 17: 250–251Google ScholarPubMed
Murrell, JC and Johnson, CB 2006 Neurophysiological techniques to assess pain in animals. Journal of Veterinary Pharmacology and Therapy 29: 325–335. https://doi.org/10.1111/j.1365-2885.2006.00758.xCrossRefGoogle ScholarPubMed
Murrell, JC, Johnson, CB, White, K, Taylor, P, Haberham, Z and Waterman-Pearson, A 2003 Changes in the EEG during castration in horses and ponies anaesthetised with halothane. Veterinary Anaesthesia and Analgesia 30: 138–146. https://doi.org/10.1046/j.1467-2995.2003.00138.xCrossRefGoogle Scholar
Murrell, JC, Mitchinson, SL, Waters, D and Johnson, CB 2007 Comparative effect of thermal, mechanical, and electrical noxious stimuli on the electroencephalogram. British Journal of Anaesthesia 98: 366–371. https://doi.org/10.1093/bja/ael377CrossRefGoogle ScholarPubMed
Murrell, JC, Mitchinson, SL, Lesperance, L, Sivakumaran, S and Johnson, CB 2010 Electroencephalography during ovario-hysterectomy in rats anaesthetized with halothane. Veterinary Anaesthesia & Analgesia 37: 14–24. https://doi.org/10.1111/j.1467-2995.2009.00504.xGoogle Scholar
Murrell, JC, White, K, Johnson, CB, Taylor, P, Doherty, T and Waterman-Pearson, A 2005 Investigation of the EEG effects of intravenous lidocaine during halothane anaesthesia in ponies. Veterinary Anaesthesia and Analgesia 32: 212–221. https://doi.org/10.1111/j.1467-2995.2005.00201.xGoogle ScholarPubMed
Newhook, JC and Blackmore, DK 1982 Electroencephalographic studies of stunning and slaughter of sheep and calves: Part 1 The onset of permanent insensibility in sheep during slaughter. Meat Science 6: 221–233. https://doi.org/10.1016/0309-1740(82)90031-6Google ScholarPubMed
Olsen, A, Keiding, S and Munk, O 2006 Effect of hypercapnia on cerebral blood flow and blood volume in pigs studied by positron emission tomography. Comparative Medicine 56: 416–420Google ScholarPubMed
Ong, R, Morris, J, O’Dwyer, J, Barnett, J, Hensworth, P and Clarke, I 1997 Behavioural and EEG changes in sheep in response to painful acute electrical stimuli. Australian Veterinary Journal 75:189–193. https://doi.org/10.1111/j.1751-0813.1997.tb10064.xCrossRefGoogle ScholarPubMed
Otto, K 2007 EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery. Laboratory Animals 42:45–61. https://doi.org/10.1258/la.2007.006025CrossRefGoogle Scholar
Otto, K and Short, CE 1991 Electroencephalographic power spectrum analysis as a monitor of anesthetic depth in horses. Veterinary Surgery 20: 362–371. https://doi.org/10.1111/j.1532-950X.1991.tb01284.xCrossRefGoogle ScholarPubMed
Racine, M, Tousignant-Laflamme, Y, Kloda, LA, Dion, D, Dupuis, G and Choiniere, M 2012 A systematic literature review of 10 years of research on sex/gender and experimental pain perception, part 1: are there really differences between women and men? Pain 153: 602–618. https://doi.org/10.1016/j.pain.2011.11.025Google ScholarPubMed
Raj, ABM 1999 Behaviour of pigs exposed to mixtures of gases and the time taken to stun and kill them: welfare implications. Veterinary Record 144: 165–168. https://doi.org/10.1136/vr.144.7.165Google Scholar
Riviere, JE and Papich, MG 2009 Veterinary Pharmacology and Therapeutics. Wiley: UKGoogle Scholar
Schwender, D, Daunderer, M, Klasing, S, Finsterer, U and Peter, K 1998 Power spectral analysis of the electroencephalo-gram during increasing end-expiratory concentrations of isoflu-rane, desflurane and sevoflurane. Anaesthesia 53: 335–342. https://doi.org/10.1046/j.1365-2044.1998.00332.xCrossRefGoogle Scholar
Siegmund, E, Cadmus, R and Lu, G 1957 A method for evalu-ating both non-narcotic and narcotic analgesics. Procedings of the Society for Experimental Biological Medicine 95: 729–731. https://doi.org/10.3181/00379727-95-23345CrossRefGoogle Scholar
Steward, JP, Ornellas, EP, Beernink, KD and Northway, WH 1968 Errors in the technique of intraperitoneal injection of mice. Applied Microbiology 16: 1418–1419CrossRefGoogle ScholarPubMed
Svendsen, O, Kok, L and Lauritzen, B 2007 Nociception after intraperitoneal injection of a sodium pentobarbitone formulation with and without lidocaine in rats quantified by expression of neu-ronal c-fos in the spinal cord‚ a preliminary study. Laboratory Animals 41: 197–203. https://doi.org/10.1258/002367707780378140CrossRefGoogle Scholar
Thomsen, C and Prior, P 1996 Quantitative EEG in assessment of anaesthetic depth: comparative study of methodology. British Journal of Anaesthesia 77: 172–178. https://doi.org/10.1093/bja/77.2.172CrossRefGoogle ScholarPubMed
Vahl, TP, Ulrich-Lai, YM, Ostrander, MM, Dolgas, CM, Elfers, EE, Seeley, RJ, D’Alessio, DA and Herman, JP 2005 Comparative analysis of ACTH and corticosterone sampling methods in rats. American Journal of Physiology - Endocrinology and Metabolism 289: E823–E828. https://doi.org/10.1152/ajpen-do.00122.2005CrossRefGoogle ScholarPubMed
Wadham, J 1997 Recognition and reduction of adverse effects in research on rodents. Faculty of Medicine and Dentistry, University of Birmingham, Birmingham, UKGoogle Scholar
Willcockson, HH, Taylor-Blake, B and Light, AR 1995 Induction of fos-like immunoreactivity by electrocutaneous stim-ulation of the rat hindpaw. Somatosensory and Motor Research 12:151–161. https://doi.org/10.3109/08990229509101506CrossRefGoogle Scholar
Wolfensohn, S and Lloyd, M 2003 Handbook of Laboratory Animal Management and Welfare, Third Edition. Blackwell Publishing Ltd: Oxford, UK. https://doi.org/10.1002/9780470751077Google Scholar
Wu, X-Y, Hu, Y-T, Guo, L, Lu, J, Zhu, Q-B, Yu, E, Wu, J-L, Shi, L-G, Huang, M-L and Bao, A-M 2015 Effect of pentobarbital and isoflurane on acute stress response in rat. Physiology & Behavior 145: 118–121. https://doi.org/10.1016/j.phys-beh.2015.04.003CrossRefGoogle ScholarPubMed
Yi, DK and Barr, GA 1995 The induction of Fos-like immunore-activity by noxious thermal, mechanical and chemical stimuli in the lumbar spinal cord of infant rats. Pain 60: 257–265. https://doi.org/10.1016/0304-3959(94)00119-YGoogle Scholar