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Relative Potency and Duration of Analgesia Following Palmar Digital Intra-Neural Alcohol Injection for Heel Pain in Horses

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Relative Potency and Duration of Analgesia Following Palmar Digital Intra-Neural Alcohol Injection for Heel Pain in Horses Relative potency and duration of analgesia following palmar digital intra-neural alcohol injection for heel pain in horses THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Christine Pariseau Schneider Graduate Program in Veterinary Clinical Sciences The Ohio State University 2013 Master's Examination Committee: Alicia Bertone, Advisor Michael Oglesbee Lisa Zekas Copyrighted by Christine Pariseau Schneider 2013 Abstract Objective: To determine the potency (percent analgesia), duration of action (up to four months), and clinical and histological effects of surgical exposure and intra-neural injection of 98% dehydrated medical-grade ethyl alcohol compared to no treatment (negative control), sham operation (surgical control), or formaldehyde injection (positive control) to decrease experimentally-induced palmar heel pain in horses. Animals: Six horses Procedures: The horses were fitted with a custom pressure-inducing shoe and had outcome measurements for each heel performed before and after nerve treatments. Outcomes included induced lameness grade and vertical peak force with pressure applied to each heel, thermal and touch sensation for each heel, and pastern circumference. Outcomes were followed serially for 112 days when nerves were harvested for histology. Results: Alcohol and formaldehyde reduced all measures of heel pain which progressed toward return, but persisted over the 112 days of the study (P<0.05). Pastern circumference was not different for alcohol than sham treatment, but was greater in formaldehyde than alcohol or baseline (P<0.05). Histological evaluation showed preservation of nerve fiber alignment with an intact epineurium, loss of axons (axon drop out), axon degeneration, fibrosis and inflammation in alcohol- and formaldehyde-injected ii nerves compared to control nerves. Formaldehyde injection induced greater fibrosis and inflammation than alcohol. Conclusions and Clinical Relevance: Alcohol injection induced effective neural blockade for months with evidence that nerve structure and function could return. Formaldehyde injection showed no advantage over alcohol and is not recommended under the conditions of our study due to soft tissue inflammation. iii I dedicate this thesis to my family and husband for their unending and inspiring support. Special thanks to my incredibly giving parents, Bob and Sheila Pariseau, for their sound advice and life-long belief in my abilities. I would not be where I am today without you! To my sister, Beth, your strength and perseverance inspire me daily to „keep swimming‟. To my husband, Tom, thank you for your unwavering and sustaining support. Your steady guidance allows me to be at my best. Thanks for holding down the fort. iv Acknowledgments I would like to thank my committee members for their guidance and assistance with the execution of this study and the formation of this thesis. A special thanks to Dr. Alicia Bertone for the dedication of many hours filled with discussion, editing, proof-reading, and teaching that made this study and thesis possible. Your guidance has been invaluable. Thank you to Dr. Michael Oglesbee and Dr. Lisa Zekas for agreeing to serve on my committee. Thank you, also, to Dr. Laurie Gallatin for her guidance through my residency and the creation of this thesis. I also wish to acknowledge and thank Akikazu Ishihara. Without his assistance, this study, the accompanying figures, and manuscript would not have been possible. I am very grateful for all of your help. v Vita June 2001 .................................................... Chelmsford High School 2005 ............................................................ B.S. Agriculture, The Ohio State University 2009 ............................................................ D.V.M., The Ohio State University 2010 to present ........................................... Graduate Teaching Associate, Department of Veterinary Medicine, The Ohio State University Fields of Study Major Field: Veterinary Clinical Sciences vi Table of Contents Abstract…………………………………………………………………………………...ii Dedication………………………………………………………………………………...iv Acknowledgements………………………………………………………………………..v Vita……………………………………………………………………………………......vi List of Figures…………………………………………………………………………...viii Chapter 1: Introduction……………………………………………………………………1 Chapter 2: Materials and Methods………………………………………………………...4 Chapter 3: Results…………………………………………………………………………9 Chapter 4: Discussion……………………………………………………………………21 Endnotes………………………………………….………………………………………24 References………………………………………………………………………………..25 vii List of Figures Figure 1. Photographs of injection procedure, custom shoe, and heat lamp.......…………8 Figure 2. Graph of baseline lameness without bolt………………………………………13 Figure 3. Graph of baseline VPF without bolt…………………………………………...14 Figure 4. Graphs of lameness grade, VPF, and percent lameness analgesia with bolt in place……………………………………………………………………………...15 Figure 5. Graphs of thermal reaction time and percent thermal analgesia…....................16 Figure 6. Graph of skin sensitivity score………………………………………………...17 Figure 7. Graph of pastern circumference across time…………………………………..18 Figure 8. Photomicrographs of sections of palmar digital nerves harvested 16 weeks post- treatment…………………………………………………………………………19 viii Chapter 1: Introduction The cost of long-term management of chronic lameness due to heel pain contributes significantly to the unwanted horse population1. Navicular syndrome2, accounts for a large percentage of chronic and incurable equine lamenesses in many breeds with an over-representation of the Quarter Horse3. Nonresponsive4 palmar heel pain has been treated by palmar digital (PD) neurectomy with reports dating back to 19625. PD neurectomy is generally reserved for the chronic, refractory cases due to the complete and long-lasting effects and risks associated with complete heel desensitization. These risks include P3 sepsis, deep digital flexor tendon rupture, luxation of the distal interphalangeal joint, hoof capsule slough, and navicular bone fracture6 as well as superficial injury due to the inability to feel the heel. Less commonly, other injuries have been managed with PD neurectomy in the athletic horse, such as distal phalanx wing fractures, sidebone, fracture of the navicular bone, and collateral ligament injuries7,8. The complication rate of PD neurectomy has decreased significantly over the last 50 years, and the latest reported incidence of neuroma formation is ~5%6. Alternate methods of neural analgesia that do not include nerve transection, might avoid neuroma formation and other potential complications6,7, but also may produce a partial or transient (weeks to months) effect that may be desirable in performance horses. 1 Medical grade ethyl alcohol is approved for perineural injection in human medicine and has been used for relief of multiple painful conditions, including trigeminal neuralgia9, ankle-foot spasticity10,11, and end-stage, intractable pain due to malignancy12,13, with reports dating back to 191214. The injections described were performed percutaneously with guidance from fluoroscopy, nerve stimulator, or computed tomography to achieve perineural injection. Relief from trigeminal neuralgia was achieved immediately post- injection in 99% of patients and mean pain-free duration was 46 months9. Reduction in ankle-foot spasticity was achieved in 90% of patients for the full 6 month follow-up period11. Relief of visceral pain caused by malignancy was achieved in 100% of patients for the first 3 months (or until death) after local infiltration of alcohol around multiple plexuses13. Although not in published literature, the American Quarter Horse Association has banned the blocking of tail motor function. Anecdotally, one substance that has been used for tail blocking is alcohol, which indicates that it has the ability to successfully block peripheral nerves in horses. Formaldehyde has been used to treat multiple disorders in the horse, including ethmoid hematomas15 and hemorrhage16 and, like alcohol, functions as a tissue fixative. Both techniques offer the potential to block nerve transduction but also preserve, in situ, the nerve structure, such as fiber alignment and the peri- and endo- neurium. By preserving peripheral nerve structure, the potential for reinnervation by nerve regeneration rather than axon sprouting with neuroma formation (as occurs after neurectomy) should be favored. 2 The primary purpose of this study was to determine the potency (percent analgesia) and duration of action (up to four months) of intra-neural injection of 98% dehydrated medical-grade ethyl alcohol as a chemical analgesic to decrease experimentally-induced palmar heel pain in the horse. Comparative groups included an untreated nerve, a sham- operated control nerve, and a nerve similarly-injected with formaldehyde. Our hypothesis was that both alcohol and formaldehyde would produce measurable analgesia for weeks and that formaldehyde would induce a greater and longer duration of analgesia than alcohol. 3 Chapter 2: Materials and Methods Experimental Design: All experimental procedures were approved and monitored by the Institutional Animal Care and Use Committee (IACUC) of The Ohio State University. Six horses purchased for research purposes and meeting inclusion criteria were fitted to a custom shoe (Figure 1A). Controlled lameness was induced at the heel of each forelimb with a bolt tightened to apply pressure to each of
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