Hostname: page-component-848d4c4894-m9kch Total loading time: 0 Render date: 2024-05-01T15:56:31.828Z Has data issue: false hasContentIssue false
  • English
  • Français

Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation

Published online by Cambridge University Press:  01 January 2023

NJ Kells ,
NJ Beausoleil ,
AE Mcllhone  and
CB Johnson
NJ Kells*
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11 -222, Palmerston North, New Zealand
NJ Beausoleil
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11 -222, Palmerston North, New Zealand
AE Mcllhone
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11 -222, Palmerston North, New Zealand 3 Dawn Rise, Glenview, Hamilton, New Zealand
CB Johnson
Affiliation:
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Private Bag 11 -222, Palmerston North, New Zealand
*
∗ Contact for correspondence and requests for reprints: N.J.Kells@massey.ac.nz
Get access Rights & Permissions [Opens in a new window]

Abstract

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior to loss of awareness. This preliminary study evaluated the electroencephalographic (EEG) responses of rats (Rattus norvegicus) to CO2 inhalation, using a method based on a minimal anaesthesia model previously used to assess nociception in mammals. Fifteen adult female Sprague-Dawley rats were anaesthetised with halothane in oxygen and maintained at a minimal plane of anaesthesia. EEG was continuously recorded throughout a 10-min baseline period followed by sequential exposure to 5, 15, 30 and 50% CO2. The EEG summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were derived from the raw EEG. The F50 of the EEG, a sensitive indicator of nociception, increased significantly above baseline during exposure to 15% CO2, suggesting this concentration was noxious to rats. This is consistent with behavioural aversion in rats at around the same CO2 concentration. Stimulation of the rat mucosal nociceptors only occurs at CO2 concentrations of 37% or greater; therefore, it is hypothesised that the observed response was a result of what would have been CO2-induced aversive respiratory sensation in conscious animals, rather than pain. This study provides some evidence that an anaesthesia model may be utilised to study the nocuous effects of low-moderate CO2 exposure in rodents.

Keywords

animal welfarecarbon dioxideelectroencephalogram (EEG)euthanasianegative affective experiencerat
Type
Articles
Information
Animal Welfare , Volume 27 , Issue 3 , August 2018 , pp. 215 - 223
Copyright
© 2018 Universities Federation for Animal Welfare

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adriaensen, H, Gybels, J, Handwerker, HO and Van Hees, J 1984 Suppression of C-fibre discharges upon repeated heat stim-ulation may explain characteristics of concomitant pain sensations. Brain Research 302: 203–211. https://doi.org/10.1016/0006-8993(84)90232-4CrossRefGoogle Scholar
Ambrose, N, Wadham, J and Morton, DB 2000 Refinement of euthanasia. In: Balls, M, van Zellar, A and Halder, M (eds) Proceedings of the 3rd World Congress on Alternatives and Animal Use in the Life Sciences pp 1159–1169. 29 August-2 September 1999, Bologna, ItalyGoogle Scholar
Banzett, RB and Moosavi, SH 2001 Dyspnoea and pain: Similarities and contrasts between two very unpleasant sensations. APS Bulletin 11: 1–8Google Scholar
Beausoleil, NJ and Mellor, DJ 2015 Introducing breathlessness as a significant animal welfare issue. New Zealand Veterinary Journal 63: 44–51. https://doi.org/10.1080/00480169.2014.940410CrossRefGoogle ScholarPubMed
Britt, DP 1987 The humaneness of carbon dioxide as an agent of euthanasia for laboratory rodents. Euthanasia of Unwanted Injured or Diseased Animals or for Educational or Scientific Purposes pp 19–31. Universities Federation for Animal Welfare: Wheathampstead, Herts, UKGoogle Scholar
Brosnan, RJ, Eger, EI, Laster, MJ and Sonner, JM 2007 Anesthetic properties of carbon dioxide in the rat. Anesthesia & Analgesia 105:103–106. https://doi.org/10.1213/01.ane.0000265556.69089.78CrossRefGoogle ScholarPubMed
Cervero, F and Merskey, H 1996 What is a noxious stimulus? Pain Forum 5: 157–161. https://doi.org/10.1016/S1082-3174(96)80020-1CrossRefGoogle 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
Chen, X, Gallar, J, Pozo, MA, Baeza, M and Belmonte, C 1995 CO2 stimulation of the cornea: A comparison between human sensation and nerve activity in polymodal nociceptive afferents of the cat. European Journal of Neuroscience 7: 1154–1163. https://doi.org/10.1111/j.1460-9568.1995.tb01105.xGoogle ScholarPubMed
Coenen, AML, Drinkenburg, WHIM, Hoenderken, R and van Luijtelaar, ELJM 1995 Carbon dioxide euthanasia in rats: oxygen supplementation minimises signs of agitation and asphyx-ia. Laboratory Animals 29: 262–268. https://doi.org/10.1258/002367795781088289CrossRefGoogle Scholar
Danneman, PJ, Stein, S and Walshaw, SO 1997 Humane and practical implications of using carbon dioxide mixed with oxygen for anaesthesia or euthanasia of rats. Laboratory Animal Science47: 376–385Google Scholar
Dominguez, CL, Barter, LS and Antognini, JF 2005 Intrathecal picrotoxin minimally alters electro-encephalographic responses to noxious stimulation during halothane and isoflurane anesthesia. Acta Anaesthesiologica Scandinavica 49: 763–770. https://doi.org/10.1111/j.1399-6576.2005.00695.xCrossRefGoogle ScholarPubMed
Dripps, RD and Comroe, JH 1947 The respiratory and circula-tory response of normal man to inhalation of 7.6 and 10.4 percent CO2 with a comparison of the maximal ventilation produced by severe muscular exercise, inhalation of CO2 and maximal volun-tary hyperventilation. American Journal of Physiology 149: 43–51. https://doi.org/10.1152/ajplegacy.1947.149.1.43CrossRefGoogle Scholar
Gerritzen, MA, Lambooij, B, Reimert, H, Stegeman, A and Spruijt, B 2004 On-farm euthanasia of broiler chickens: effects of different gas mixtures on behavior and brain activi-ty. Poultry Science 83: 1294–1301. https://doi.org/10.1093/ps/83.8.1294CrossRefGoogle Scholar
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/10.1080/00480169.2009.36882CrossRefGoogle Scholar
Gracely, RH, Undem, BJ and Banzett, RB 2007 Cough, pain and dyspnoea: similarities and differences. Pulmonary Pharmacology and Therapeutics 20: 433–437. https://doi.org/10.1016/j.pupt.2006.12.005CrossRefGoogle ScholarPubMed
Hawkins, P, Playle, L, Golledge, H, Leach, M, Banzett, R, Coenen, A, Cooper, J, Danneman, P, Flecknell, P, Kirkden, R, Niel, L and Raj, M 2006 Newcastle consensus meeting on carbon dioxide euthanasia of laboratory animals. University of Newcastle upon Tyne, Newcastle, UKGoogle Scholar
IASP Task Force on Pain Taxonomy 1994 Part III: pain terms, a current list with definitions and notes on usage. In: Merskey, H and Bogduk, N (eds) Classification of Chronic Pain pp 209–214. IASP Press: Seattle, USAGoogle Scholar
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
Jones, M, Berwick, J, Hewson-Stoate, N, Gias, C and Mayhew, J 2005 The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation. NeuroImage 27: 609–623. https://doi.org/10.1016/j.neuroim-age.2005.04.036CrossRefGoogle ScholarPubMed
Lansing, RW, Gracely, RH and Banzett, RB 2009 The multi-ple dimensions of dyspnea: Review and hypothesis. Respiratory Physiology & Neurobiology 167: 53–60. https://doi.org/10.1016/j.resp.2008.07.012CrossRefGoogle Scholar
Leach, MC, Bowell, VA, Allan, TF and Morton, DB 2002 Degrees of aversion shown by rats and mice to different concen-trations of inhalational anaesthetics. Veterinary Record 150: 808–815. https://doi.org/10.1136/vr.150.26.808CrossRefGoogle Scholar
Leach, MC, Bowell, VC, Allan, TF and Morton, DB 2004 Measurement of aversion to determine humane methods of anaesthesia and euthanasia. Animal Welfare 13: 77–86Google 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
Liotti, M, Brannan, S, Egan, G, Shade, R, Madden, L, Abplanalp, B, Robillard, R, Lancaster, J, Zamarripa, FE, Fox, PT and Denton, D 2001 Brain responses associated with con-sciousness of breathlessness (air hunger). Proceedings of the National Academy of Sciences of the United States of America 98:2035–2040. https://doi.org/10.1073/pnas.98.4.2035CrossRefGoogle Scholar
Makowska, IJ, Vickers, L, Mancell, J and Weary, DM 2009 Evaluating methods of gas euthanasia for laboratory mice. Applied Animal Behaviour Science 121: 230–235. https://doi.org/10.1016/j.applanim.2009.10.001CrossRefGoogle Scholar
Martoft, L, Lomholt, L, Kolthoff, C, Rodriguez, BE, Jensen, EW, Jorgensen, PF, Pedersen, HD and Forslid, A 2002 Effects of CO2 anaesthesia on central nervous system activity in swine. Laboratory Animals 36: 115–126. https://doi.org/10.1258/0023677021912398CrossRefGoogle ScholarPubMed
Mellema, MS 2008 The neurophysiology of dyspnea. Journal of Veterinary Emergency and Critical Care 18: 561–571. https://doi.org/10.1111/j.1476-4431.2008.00372.xCrossRefGoogle Scholar
Murrell, J, Mitchinson, SL, Waters, D and Johnson, CB 2007 Comparative effect of thermal, mechanical, and electrical noxious stimuli on the electroencephalogram of the rat. British Journal of Anaesthesia 98: 366–371. https://doi.org/10.1093/bja/ael377CrossRefGoogle 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, Waters, D and Johnson, CB 2008 Comparative effects of halothane, isoflurane, sevoflurane and desflurane on the electroencephalogram of the rat. Laboratory Animals 42: 161–170. https://doi.org/10.1258/la.2007.06019eCrossRefGoogle ScholarPubMed
Niel, L, Stewart, SA and Weary, DM 2008 Effect of flow rate on aversion to gradual-fill carbon dioxide exposure in rats. Applied Animal Behaviour Science 109: 77–84. https://doi.org/10.1016/j.applanim.2007.02.004CrossRefGoogle Scholar
Niel, L and Weary, D 2007 Rats avoid exposure to carbon diox-ide and argon. Applied Animal Behaviour Science 107: 100–109. https://doi.org/10.1016/j.applanim.2006.08.002CrossRefGoogle Scholar
Niel, L and Weary, DM 2006 Behavioural responses of rats to gradual-fill carbon dioxide euthanasia and reduced oxygen con-centrations. Applied Animal Behaviour Science 100: 295–308. https://doi.org/10.1016/j.applanim.2005.12.001CrossRefGoogle Scholar
Ong, R, Morris, J, O’Dwyer, J, Barnett, J, Hemsworth, 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
Orth, M, Barter, L, Dominguez, C, Atherley, R, Carstens, E and Antognini, JF 2005 Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation. British Journal of Anaesthesia 95: 477–484. https://doi.org/10.1093/bja/aei208CrossRefGoogle ScholarPubMed
Peppel, P and Anton, F 1993 Responses of rat medullary dorsal horn neurons following intranasal noxious chemical stimulation: effects of stimulus intensity, duration, and interstimulus interval. Journal of Neurophysiology 70: 2260–2275. https://doi.org/10.1152/jn.1993.70.6.2260CrossRefGoogle ScholarPubMed
Schön D, Dahme B and Leupoldt Av 2008 Associations between the perception of dyspnea, pain, and negative affect. Psychophysiology 45: 1064–1067. https://doi.org/10.1111/j.1469-8986.2008.00704.xCrossRefGoogle Scholar
Smith, W and Harrap, SB 1997 Behavioural and cardiovascular responses of rats to euthanasia using carbon dioxide gas. Laboratory Animals 31: 337–346. https://doi.org/10.1258/002367797780596130Google ScholarPubMed
Steriade, M, Amzica, F and Contreras, D 1994 Cortical and thalamic cellular correlates of electroencephalographic burst-sup-pression. Electroencephalography and Clinical Neurophysiology 90: 1–16. https://doi.org/10.1016/0013-4694(94)90108-2Google 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
Thurauf, N, Friedel, I, Hummel, C and Kobal, G 1991 The mucosal potential elicited by noxious chemical stimuli with CO2 in rats: is it a peripheral nociceptive event? Neuroscience Letters 128: 297–300. https://doi.org/10.1016/0304-3940(91)90283-YCrossRefGoogle ScholarPubMed
Thurauf, N, Hummel, T, Kettenmann, B and Kobal, G 1993 Nociceptive and reflexive responses recorded from the human nasal mucosa. Brain Research 629: 293–299. https://doi.org/10.1016/0006-8993(93)91333-NCrossRefGoogle ScholarPubMed
Thurmon, J, Tranquilli, W and Benson, G 1996 Lumb & Jones’ Veterinary Anesthesia, Third Edition. Williams & Wilkins: Baltimore, USAGoogle Scholar
Vollmer, LL, Ghosal, S, McGuire, JL, Ahlbrand, RL, Li, K-Y, Santin, JM, Ratliff-Rang, CA, Patrone, LGA, Rush, J, Lewkowich, IP, Herman, JP, Putnam, RW and Sah, R 2016 Microglial acid sensing regulates carbon dioxide-evoked fear. Biological Psychiatry 80: 541–551. https://doi.org/10.1016/j.biopsych.2016.04.022CrossRefGoogle ScholarPubMed
von Leupoldt, A and Dahme, B 2005 Differentiation between the sensory and affective dimension of dyspnea during resistive load breathing in normal subjects. Chest 128: 3345–3349. https://doi.org/10.1378/chest.128.5.3345CrossRefGoogle ScholarPubMed
von Leupoldt, A, Sommer, T, Kegat, S, Baumann, HJ, Klose, H, Dahme, B and B'chel, C 2009 Dyspnea and pain share emotion-related brain network. NeuroImage 48: 200–206. https://doi.org/10.1016/j.neuroimage.2009.06.015CrossRefGoogle ScholarPubMed
Williams, DC, Brosnan, RJ, Fletcher, DJ, Aleman, M, Holliday, TA, Tharp, B, Kass, PH, LeCouteur, RA and Steffey, EP 2016 Qualitative and quantitative characteristics of the electroencephalogram in normal horses during administration of inhaled anesthesia. Journal of Veterinary Internal Medicine 30:289–303. https://doi.org/10.1111/jvim.13813Google ScholarPubMed
Yoshitani, K, Kawaguchi, M, Takahashi, M, Kitaguchi, K and Furuya, H 2003 Plasma propofol concentration and EEG burst suppression ratio during normothermic cardiopulmonary bypass. British Journal of Anaesthesia 90: 122–126. https://doi.org/10.1093/bja/aeg010Google ScholarPubMed
Ziemann, A, Allen, J, Dahdaleh, NS, Drebot, I, Coryell, M, Wunsch, A, Lynch, C, Faraci, F, Howard, M, Welsh, M and Wemmie, J 2009 The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behaviour. Cell 139: 1012–1021CrossRefGoogle Scholar