ANNE BAHRENBERG M U I S E N Antinociceptive effects of epidural magnesium G A sulphate alone or in combination with M morphine in dogs F O S T C E F F E E V I T P E C I C O N I T N A G R E B N E R H A Inauguraldissertation zur Erlangung des Grades eines édition scientifique B VVB LAUFERSWEILER VERLAG E Dr. med. vet. N beim Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen VVB LAUFERSWEILER VERLAG N STAUFENBERGRING 15 ISBN: 978-3-8359-6269-9 A D-35396 GIESSEN Tel: 0641-5599888 Fax: -5599890 [email protected] www.doktorverlag.de 9 783835 962699 édition scientifique Photo cover: © Andrey Prokhorov - iStockPhoto VVB LAUFERSWEILER VERLAG VVB Das Werk ist in allen seinen Teilen urheberrechtlich geschützt. Die rechtliche Verantwortung für den gesamten Inhalt dieses Buches liegt ausschließlich bei dem Autor dieses Werkes. Jede Verwertung ist ohne schriftliche Zustimmung des Autors oder des Verlages unzulässig. Das gilt insbesondere für Vervielfältigungen, Übersetzungen, Mikroverfilmungen und die Einspeicherung in und Verarbeitung durch elektronische Systeme. 1. Auflage 2014 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the Author or the Publishers. 1st Edition 2014 © 2014 by VVB LAUFERSWEILER VERLAG, Giessen Printed in Germany édition scientifique VVB LAUFERSWEILER VERLAG STAUFENBERGRING 15, D-35396 GIESSEN Tel: 0641-5599888 Fax: 0641-5599890 email: [email protected] www.doktorverlag.de Faculty of Veterinary Medicine, Clinic of Small Animal, Surgery Justus-Liebig-University Giessen, Germany Prof. Dr. Sabine Tacke and Faculty of Veterinary Science, Department of Companion Animal Clinical Studies University of Pretoria, South Africa Dr. Eva Rioja-Garcia Antinociceptive effects of epidural magnesium sulphate alone or in combination with morphine in dogs INAUGURAL DISSERTATION for the acquisition of the doctoral degree at the Faculty of Veterinary Medicine Justus-Liebig-University Giessen, Germany submitted by Anne Bahrenberg Veterinarian from Dortmund Giessen 2014 With permission of the Faculty of Veterinary Medicine of Justus-Liebig-University Giessen Dean: Prof. Dr. Dr. h.c. Martin Kramer Referee 1: Prof. Dr. Sabine Tacke Referee 2: Prof Dr Joachim Geyer Day of Disputation: 4th November 2014 Table of contents Table of contents Table of contents ................................................................................................................ I Declaration ....................................................................................................................... III Acknowledgements .......................................................................................................... IV Abbreviations .................................................................................................................. VI List of Figures ............................................................................................................... VIII List of Tables .................................................................................................................... X 1 Introduction ....................................................................................................... 1 2 Literature review ............................................................................................... 4 2.1 Pain ..................................................................................................................... 4 2.1.1 The definition of pain .......................................................................................... 4 2.1.2 Peripheral nociception ......................................................................................... 5 2.1.3 Central nociception .............................................................................................. 7 2.1.4 Classification of pain ......................................................................................... 15 2.1.5 Physiological consequences of pain .................................................................. 19 2.2 Pain management ............................................................................................ 23 2.2.1 Epidural analgesia .............................................................................................. 23 2.3 Magnesium ....................................................................................................... 30 2.3.1 Magnesium physiology ...................................................................................... 30 2.3.2 Magnesium as a systemic analgesic .................................................................. 35 2.3.3 Magnesium as a neuraxial analgesic .................................................................. 36 2.4 Types of threshold testing ............................................................................... 40 2.4.1 Mechanical threshold testing ............................................................................. 43 3 Objectives and Hypotheses ............................................................................. 47 3.1 Objectives ......................................................................................................... 47 3.1.1 Primary objectives ............................................................................................. 47 3.1.2 Secondary objectives ......................................................................................... 47 3.2 Hypotheses ........................................................................................................ 47 3.2.1 Primary hypotheses ............................................................................................ 47 3.2.2 Secondary hypotheses ........................................................................................ 48 4 Material and Methods ..................................................................................... 49 I Table of contents 4.1 Dogs ................................................................................................................... 49 4.2 Study design ..................................................................................................... 49 4.2.1 Anaesthesia ........................................................................................................ 50 4.2.2 Epidural catheter placement and drug administration ....................................... 50 4.2.3 Antinociceptive threshold testing using the von Frey device ............................ 51 4.2.4 Additional measurements .................................................................................. 55 4.3 Statistical analysis ............................................................................................ 56 5 Results ............................................................................................................... 58 5.1 Dogs ................................................................................................................... 58 5.2 Anaesthesia, epidural catheter placement and drug administration .......... 58 5.3 Antinocicpetive threshold testing using the von Frey device ....................... 59 5.3.1 Repeatability of the von Frey threshold ............................................................. 59 5.3.2 Antinocicpetive effects of the treatments .......................................................... 60 5.3.3 Changes in the antinociceptive threshold over time for regions ........................ 63 5.3.4 Changes in the antinociceptive threshold over time for treatments ................... 65 5.3.5 Changes in the antinociceptive thresholds over time in individual dogs for each treatment ............................................................................................................ 73 5.3.6 Effect of side on the thresholds ......................................................................... 80 5.4 Additional measurements ............................................................................... 80 5.4.1 Sedation ............................................................................................................. 80 5.4.2 Behaviour........................................................................................................... 81 5.4.3 Motor effects ...................................................................................................... 82 5.4.4 Room temperature and humidity ....................................................................... 82 6 Discussion ......................................................................................................... 83 7 Conclusion ........................................................................................................ 92 8 Summary .......................................................................................................... 93 9 Zusammenfassung ........................................................................................... 95 10 References......................................................................................................... 97 II Declaration Declaration I declare that I have completed this dissertation without the unauthorized help of a second party and only with the assistance acknowledged therein. I have appropriately acknowledged and referenced all text passages that are derived literally from or are based on content of published or unpublished work of others, and all information that relates to verbal communications. I have abided by the principle of good scientific conduct laid down in the charter of the Justus-Liebig-University of Giessen in carrying out the investigations described in the dissertation. Giessen, Anne Bahrenberg III Acknowledgements Acknowledgements I would like to thank, Dr Eva Rioja Garcia, for her trust in me, guidance, inexhaustible enthusiasm and support during the whole project and beyond that. For introducing me into the world of research. Dr. Sabine Tacke, for her willingness to support my external project. Prof Geoffrey Fosgate for his patience explaining me statistics, his motivation and ideas. Dr. Brighton Dzikiti, for his helping hand during data collection. The staff at the University of Pretoria Biomedical Research Centre for their help and support. Mrs Kerstin Küster for helping me with the format and computer related queries. My parents for their immeasurable support. IV Acknowledgements In Erinnerung an meine Groβeltern V Abbreviations Abbreviations % Percent AB Anne Bahrenberg ACTH Adrenocorticotrophic hormone ACVA American College of Veterinary Anesthesiologists AMPA Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid BD Brighton Dzikiti Cm Centimetre CNS Central nervous system Co Control treatment CO Carbon dioxide 2 Cp Carpal pad CRF Corticotrophin releasing factor CRI Constant rate infusion CSF Cerebrospinal fluid ER Eva Rioja-Garcia G Gauge gr Gram GABA Gamma-aminobutyric acid IQR Interquartile range IV Intravenous JCAHO Joint Commission on Accreditation of Healthcare Organisations kg Kilograms Mt Metatarsus mg Milligrams Mg Magnesium treatment Mg2+ Ionized magnesium MgSO Magnesium sulphate 4 Mm Magnesium and morphine treatment Mo Morphine treatment mL Millilitre VI
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