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Hormone Induced Migraine and Attempts at Blocking Opiate Reward Through Nk1

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Hormone Induced Migraine and Attempts at Blocking Opiate Reward Through Nk1 Hormone Induced "Migraine" and Attempts at Blocking Opiate Reward through NK1 Item Type text; Electronic Dissertation Authors Skinner, David P. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 07/10/2021 05:59:45 Link to Item http://hdl.handle.net/10150/321547 HORMONE INDUCED MIGRAINE AND ATTEMPTS AT BLOCKING OPIATE REWARD THROUGH NK1 David P. Skinner, Jr. ______________________________________ Copyright © David P. Skinner, Jr. 2014 A Dissertation to the Faculty of the DEPARTMENT OF PHARMACOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2014 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by David P. Skinner, Jr. entitled, Hormone Induced “Migraine” and Attempts at Blocking Opiate Reward through NK1 and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy _________________________________________________________________________ Date: 05/08/2014 Todd W. Vanderah, Ph.D. _________________________________________________________________________ Date: 05/08/2014 Edward D. French, Ph.D. _________________________________________________________________________ Date: 05/08/2014 John Bloom, M.D. _________________________________________________________________________ Date: 05/08/2014 Victor J. Hruby, Ph.D. Final approval and acceptance of this dissertating is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. _________________________________________________________________________ Date: 05/08/2014 Dissertation Director: Todd W. Vanderah 2 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of the requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that an accurate acknowledgement of the source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the copyright holder. Signed: David P. Skinner, Jr. 3 ACKNOWLEDGEMENTS As I start to compile and write this document that will forever reflect the work I participated in and data I helped to generate while working under the direction of Dr. Todd W. Vanderah, I am forced to reflect on the past 4 years in my Ph.D. First, I have to thank Dr. Vanderah for taking me on as a medical student in the beginning and allowing me to grow into the role as a Ph.D. student. It has been a pleasure to work with him and for him and I am extremely thankful for the opportunity I have had to challenge myself throughout these years and learn to think more critically and ask those hard “Why” questions in Science. Second, I would like to thank Dr. Greg Dussor for always making himself available to discuss anything with me. He has been a great mentor and has become a very close friend. I appreciate how generous he was with his time and how genuine he was with his critiques and suggestions on how I could become a better scientist. I am truly a better person and a better scientist having opportunity to work with both Dr. Vanderah and Dr. Dussor over the past 4 years and for this I will be forever grateful. I also would like to acknowledge my committee members Dr. John Bloom, Dr. Edward D. French, and Dr. Victor J. Hruby, for being so supportive and helpful throughout this entire journey. There willingness to come to my seminars and alter their busy schedules to assist in this committee process is most appreciated. My lab members both past and present, Tally M. Largent-Milnes, Katherine Hanlon, Ashley Liguori, Lauren Slosky, Lynn Bui, and Warren Wang have been a tremendous 4 support in my tenure here. I have enjoyed learning from and teaching on occasion each and everyone one of them. Lastly, I would like to acknowledge the most important person in my life, a partner, and my biggest supporter. Over the past 14 years of our lives together she has helped me chase my dreams and accomplish my goals all, while raising our four beautiful children and working on her own personal goals. She is a wonderful woman, and the love of my life. 5 DEDICATION I dedicate this manuscript to my children; Jordan, Jaycie, Caden and Hadley but most of all to my beautiful wife! Thank you for being a constant force in my life that makes me strive to be a better person each and every day. “If you can’t explain it simply, you don’t understand it well enough.” Albert Einstein 6 Table of Contents STATEMENT BY AUTHOR .................................................................................................................... 3 ACKNOWLEDGEMENTS ........................................................................................................................ 4 DEDICATION ............................................................................................................................................ 6 LIST OF FIGURES ................................................................................................................................ 9 LIST OF TABLES ................................................................................................................................. 10 ABSTRACT FOR HORMONE INDUCED MIGRAINE ............................................................ 11 ABSTRACT FOR NK1 ......................................................................................................................... 12 LIST OF ABBREVIATIONS ............................................................................................................. 14 CHAPTER 1: INTRODUCITON AND BACKGROUND ........................................................... 17 PAIN ......................................................................................................................................................................... 17 Chronic (Neuropathic) Pain .......................................................................................................................... 17 Migraine ................................................................................................................................................................ 20 THERAPEUTICS ....................................................................................................................................................... 23 Treatments for Chronic Pain, drug classes, procedures ................................................................... 23 Treatments for Migraine, drug classes, procedures ........................................................................... 26 SIDE EFFECTS AND LIMITATIONS ........................................................................................................................ 28 Chronic Pain Therapies ................................................................................................................................... 28 RECEPTORS AND LIGANDS .................................................................................................................................... 30 Tachykinin Peptides and their Neurokinin Receptors ....................................................................... 30 Estrogen: Receptors and Ligands ............................................................................................................... 32 SIGNIFICANCE AND HYPOTHESIS ......................................................................................................................... 33 Chronic Pain Treatment ................................................................................................................................. 33 Hormone Related Migraine ........................................................................................................................... 36 CHAPTER 2: MATERIALS AND METHODS ............................................................................. 39 ANIMALS .................................................................................................................................................................. 39 2.11 NK1 Animals ............................................................................................................................................... 39 2.12 CSD Animals ............................................................................................................................................... 39 2.2 SURGICAL PROCEDURES ................................................................................................................................. 39 2.21 NK1 surgeries ............................................................................................................................................ 39 2.22 CSD Surgeries ...........................................................................................................................................
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