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Thesis Formatted Identifying and Treating Neuropathic Pain in Dogs with Syringomyelia Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Ashley C. Hechler, DVM Graduate Program in Comparative Veterinary Medicine The Ohio State University 2019 Thesis Committee Sarah A. Moore, DVM, MS, DACVIM, Advisor Lynette K. Cole, DVM, DACVD Laurie B. Cook, DVM, DACVIM Eric T. Hostnik, DVM, MS, DACVR Copyrighted by Ashley C. Hechler, DVM 2019 Abstract Syringomyelia (SM) is a debilitating condition in the cavalier King Charles spaniel (CKCS) that results in neuropathic pain and diminished quality of life. Von Frey aesthesiometry (VFA) is a method of mechanical quantitative sensory testing that provides an objective sensory threshold (ST) value and can be used to quantify neuropathic pain and monitor response to therapy. The utility of VFA has been previously established in client-owned dogs with acute spinal cord injury and osteoarthritis but the technique has not been evaluated in dogs with SM. The goal of this study was to evaluate ST, as determined by VFA, in dogs with and without SM, to assess the utility of VFA in quantifying NP in SM-affected dogs. We hypothesized the SM- affected CKCS would have lower ST values consistent with hyperesthesia, when compared to control CKCS. Additionally, we hypothesized that ST values in SM-affected dogs would be inversely correlated with syrinx size on MRI and with owner-derived clinical sign scores. ST values for the thoracic and pelvic limbs differed significantly between SM-affected and control CKCS (p=0.027; p=0.0396 respectively). Median ST value (range) for the thoracic limbs was 184.1 grams (120.9-552) for control dogs, and 139.9 grams (52.6- ii 250.9) for SM-affected dogs. The median ST value (range) for the pelvic limbs was 164.9 grams (100.8-260.3) in control dogs and 129.8 grams (57.95-168.4) in SM-affected dogs. The ST values in SM-affected dogs did not correlate with syrinx height on MRI (r=0.314; p=0.137). Owner-reported clinical sign scores showed an inverse correlation with pelvic limb ST values, where dogs with lower ST values (hyperesthesia) were reported by their owners to display more frequent and severe clinical signs (r=-0.657; p=0.022). ST values were lower in SM-affected CKCS compared to control dogs, suggesting the presence of neuropathic pain. Dogs with lower ST pelvic limb values were perceived by their owners to have more severe clinical signs classically associated with SM. Our results suggest that VFA may offer an objective assessment of neuropathic pain in SM- affected dogs and could be useful for monitoring response to therapy in future clinical studies. iii Dedication In dedication to Maverick, my childhood cavalier King Charles Spaniel, whose lifelong battle with Chiari-like malformation and syringomyelia fueled my desire to help others like him by becoming a veterinary neurologist. To my fiancé Stephen Jones, our CKCS Patrick, and golden retriever Finnegan, who have been a constant source of love and encouragement throughout my life, especially while in pursuit of my graduate degree. I also dedicate this thesis to my family for their unrelenting support over the years. iv Acknowledgments I wish to thank my advisor and mentor, Dr. Sarah Moore for her guidance and support throughout this entire process. I would also like to thank Dr. Cole, Dr. Cook and Dr. Hostnik for their expertise and assistance as members of my masters committee. I gratefully acknowledge Ms. Amanda Disher, Ms. Heather Anderson, Ms. Lane Bookenberger, and Ms. Josey Sobolewski for their assistance with patient care and data collection. Finally, I would like to thank all the clients and cavalier King Charles spaniels that offered their time and support to the project. v Vita May 2006….……………………………….. Father Lopez Catholic High School May 2010…………………………………... B.S. Animal Science, Clemson University May 2015…………………………..………. D.V.M., University of Florida 2015 to 2016…………………...…………... Intern, Metropolitan Veterinary Hospital 2016 to present……………………………... Residency in Neurology and Neurosurgery, Veterinary Medical Center, The Ohio State University Publications 1. Black LJ, Hechler AC, Duffy ME, and Beatty SSK. "Presumed lupus erythematosus cells identified in bronchoalveolar lavage fluid from a Mexican Hairless dog." Veterinary Clinical Pathology. 2017; 46 (2): 354-359 2. Hechler AC, Moore SA. “Understanding and treating Chiari-like malformation and syringomyelia in dogs.” Topics in Companion Animal Medicine. 2018; 33(1):1-11 vi Fields of Study Major Field: Comparative Veterinary Medicine vii Table of Contents Abstract .......................................................................................................................... ii Dedication ...................................................................................................................... iv Acknowledgments ........................................................................................................... v Vita ................................................................................................................................ vi Publications ................................................................................................................... vi Fields of Study .............................................................................................................. vii List of Tables ................................................................................................................. xi List of Figures .............................................................................................................. xiii List of Abbreviations.................................................................................................... xvi Chapter 1. Introduction ................................................................................................... 1 Chapter 2. Literature Review .......................................................................................... 3 2.1. Craniocervical Junction ........................................................................................ 3 2.1.1. Craniocervical Junction Anatomy .................................................................. 3 2.1.2. Craniocervical Junction Anomalies ................................................................ 5 viii 2.2 Syringomyelia ..................................................................................................... 16 2.2.1. Classification of Syringomyelia ................................................................... 16 2.2.1 Cerebrospinal Fluid Flow .............................................................................. 17 2.2.2 Etiology and Pathogenesis ............................................................................ 18 2.3. Clinical Presentation ........................................................................................... 21 2.3.1. Signalment ................................................................................................... 21 2.3.2. Clinical Signs .............................................................................................. 22 2.3.3. Diagnostics .................................................................................................. 27 2.3. Pain .................................................................................................................... 32 2.3.1. Classification of Pain ................................................................................... 34 2.3.2 Substance P .................................................................................................. 36 2.4. Quantitative Sensory Testing .............................................................................. 38 2.4.1. Von Frey Anesthesiometry........................................................................... 40 2.4.2. Alternative Quantitative Sensory Testing in Veterinary Medicine ................ 42 2.5. Treatment ........................................................................................................... 43 2.5.1. Medical Management................................................................................... 43 2.5.2. Surgical Management .................................................................................. 53 2.5.3. Alternative Therapies ................................................................................... 54 ix 2.6. Prognosis ............................................................................................................ 56 Chapter 3. Mechanical quantitative sensory testing in Cavalier King Charles Spaniels with and without syringomyelia .................................................................................... 59 3.1. Abstract .............................................................................................................. 59 3.2. Introduction ........................................................................................................ 61 3.3. Results................................................................................................................ 63 3.4. Discussion .......................................................................................................... 70 3.5. Conclusion ......................................................................................................... 74 3.6. Materials and Methods ......................................................................................
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