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The Neurophysiological Basis of the Divergent Sympathetic Responses to Long-Lasting Experimental Muscle Pain in Humans

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The Neurophysiological Basis of the Divergent Sympathetic Responses to Long-Lasting Experimental Muscle Pain in Humans THE NEUROPHYSIOLOGICAL BASIS OF THE DIVERGENT SYMPATHETIC RESPONSES TO LONG–LASTING EXPERIMENTAL MUSCLE PAIN IN HUMANS Sophie Kobuch (BA, BMedRes) School of Medicine Western Sydney University Supervisor: Professor Vaughan Macefield Co-supervisor: Associate Professor Luke Henderson Co-supervisor: Doctor Rachael Brown A thesis submitted to Western Sydney University in fulfilment of the requirements of Doctor in Philosophy 2018 Acknowledgments The list of people who have encouraged me throughout my PhD is endless. Family, friends, partner, supervisors, colleagues, participants, you name it. These few words do not reflect the least of their help. Thank you to all participants, most of whom were my friends and colleagues, who have endured sitting or lying still for hours while being in pain. Thank you to the University of Sydney Neuroimaging lab for being a fun group to be around, and for including me in your team. Andrew, thanks for teaching me all the very basics of neuroimaging, you deserve a double PhD with all the time and effort you have devoted to helping me. I look forward to the next-generation “Macefield-Henderson!” Emily, thank you for all the nerdy chats, coffee breaks, climbing sessions, it’s been so fun! Flav, you have become one of my closest friends. I thank you for all the discussions – whether they were science based, political, or other. Your knowledge and work ethic have made me a better person and a better scientist. Zeynab, thank you for the great discussions, fun times, and lunches. Noemi and Kasia, thanks for making the windowless office a fun place to work in. Beatriz, thank you for being always in such a great mood, your positivity and laughter are always so uplifting. I will miss practicing my couple of words of Spanish with you! Azza, thank you for finding the divergent response to muscle pain! I have truly enjoyed stepping into your shoes and leading this project, and continuing a great collaboration with you. Thank you to my family, I could not have dreamt of a better one. Your constant support has allowed me to pursue my wildest dreams, getting a PhD being one of them. Steph and Christoph, thank you so much for your help formatting this thesis. To my Aussie parents, Tonny and Peter, thank you for all your support since the first weekend I set foot on this continent. Your love and support has made living away from home a lot easier. Richard, no words can describe how lucky I am to be sharing my life with you. Your help throughout my PhD has been tremendous, thank you for everything. Rachael, thank you for all your support throughout the last four years. You have always been here for me, and have pushed me through good and bad times. I really appreciate your guidance and help all along. Luke, I’m sorry for being the most annoying PhD student you have ever had! I cannot thank you enough for all your time, effort, and expertise. I could not have done any of it without your constant guidance. I have grown and learned so much under your supervision and feel privileged to have worked with you. Vaughan, thank you for your positivity and for your endless passion, energy, and wisdom. I am extremely lucky to have had your confidence to take on this incredible opportunity. I am grateful for our friendship, and for all the times you have made me feel at home in a place far away from home. Statement of Authentication The work presented in this thesis is, to the best of my knowledge and belief, original except as acknowledged in the text. I hereby declare that I have not submitted this material, either in full or in part, for a degree at this or any other institution. Signature Publications arising from this thesis Kobuch, S., Fazalbhoy, A., Brown, R., Macefield, V.G. (2015). Inter-individual responses to experimental muscle pain: Baseline physiological parameters do not determine whether muscle sympathetic nerve activity increases or decreases during pain. Front Neurosci 9: 471. (Appendix A) Kobuch, S., Fazalbhoy, A., Brown, R., Macefield, V.G. (2016). Inter-individual responses to experimental muscle pain: Baseline anxiety ratings and attitudes to pain do not determine the direction of the sympathetic response to tonic muscle pain in humans. Int J Psychophysiol 104: 17–23. (Chapter 3) Kobuch, S., Fazalbhoy, A., Brown, R., Henderson, L.A., Macefield, V.G. (2017). Central circuitry responsible for the divergent sympathetic responses to tonic muscle pain in humans. Hum. Brain Mapp. 38: 869-881. (Chapter 4) Kobuch, S., Fazalbhoy, A., Brown, R., Macefield, V.G., Henderson, L.A. (2017): Muscle sympathetic nerve activity-coupled changes in brain activity during sustained muscle pain. Brain & Behaviour. 8: e00888 (Chapter 5) Kobuch, S., Henderson, L.A., Macefield, V.G., Brown, R. (2018): The effects of audio-visual distraction on the muscle sympathetic responses to experimental muscle pain. Experimental Brain Research. 236: 1919-1925 (Chapter 6) Table of Contents LIST OF TABLES ............................................................................................................................... VI LIST OF FIGURES ........................................................................................................................... VII LIST OF ABBREVIATIONS .............................................................................................................. X ABSTRACT ........................................................................................................................................ 13 CHAPTER 1 INTRODUCTION ................................................................................................................. 15 1.1. Autonomic nervous system ................................................................................................... 16 1.1.1. Sympathetic nervous system.............................................................................................................................. 17 1.1.2. Parasympathetic nervous system .................................................................................................................... 20 1.2. The arterial baroreflex........................................................................................................... 22 1.3. Muscle sympathetic nerve activity .................................................................................... 25 1.4. Supraspinal regulation of MSNA ........................................................................................ 28 1.4.1. Animal studies ............................................................................................................................................................ 28 1.4.2. Human studies............................................................................................................................................................ 29 1.5. Noxious stimulation ................................................................................................................ 31 1.6. Pain and the sympathetic nervous system ..................................................................... 32 1.6.1. Animal studies ............................................................................................................................................................ 33 1.6.2. Human studies............................................................................................................................................................ 34 1.6.3. Supraspinal regulation........................................................................................................................................... 36 1.7. Microneurography ................................................................................................................... 38 1.7.1. Sympathetic microneurography ....................................................................................................................... 39 1.7.2. Analysis .......................................................................................................................................................................... 40 1.8. Imaging of central cardiovascular control .................................................................... 41 i 1.8.1. MSNA-coupled fMRI ................................................................................................................................................ 43 1.9. Aims & Hypotheses................................................................................................................... 44 CHAPTER 2 GENERAL METHODS ........................................................................................................ 47 2.1. General procedures ................................................................................................................. 48 2.1.1. MSNA recording procedures .............................................................................................................................. 48 2.1.2. Noxious stimulation protocol............................................................................................................................. 50 2.1.3. MSNA-coupled fMRI ................................................................................................................................................ 51 2.2. Analytical procedures ............................................................................................................. 52 2.2.1. MSNA and cardiorespiratory parameters ..................................................................................................
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