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A reproducible model for long-term rehabilitation of the foundered equine metabolic syndrome horse
870
Abstracts / Journal of Equine Veterinary Science 33 (2013) 860-883
References [1] van Eps AW, Pollitt CC. Equine laminitis model: lamellar histopathology seven days after induction with oligofructose. Equine Vet J 2009;41:735–40. [2] Jones E, Vinuela-Fernandez I, Eager RA, et al. Neuropathic changes in equine laminitis pain. Pain 2007;132:321–31. [3] Morgan SJ, Grosenbaugh DA, Hood DM. The pathophysiology of chronic laminitis. Pain and anatomic pathology. Vet Clin North Am Equine Pract 1999;15:395–417. [4] van Eps AW, Leise BS, Watts M, Pollitt CC, Belknap JK. Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model. Equine Vet J 2012;44:230–7. [5] Belknap JK, Giguere S, Pettigrew A, Cochran AM, van Eps AW, Pollitt CC. Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response. Equine Vet J 2007;39: 42–7. [6] Fontaine GL, Belknap JK, Allen D, Moore JN, Kroll DL. Expression of interleukin-1beta in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. Am J Vet Res 2001;62: 714–20. [7] Pollitt CC. Basement membrane pathology: a feature of acute equine laminitis. Equine Vet J 1996;28:38–46. [8] Abrahamsen EJ. How to manage acute pain in laminitis. In: Proceedings of the Congress of the British Equine Veterinary Association. Birmingham: Equine Veterinary Journal Ltd.; 2005: 195–6. [9] Harding LM, Kristensen JD, Baranowski AP. Differential effects of neuropathic analgesics on wind-up-like pain and somatosensory function in healthy volunteers. Clin J Pain 2005;21:127–32. [10] Arendt-Nielsen L, Frokjaer JB, Staahl C, et al. Effects of gabapentin on experimental somatic pain and temporal summation. Reg Anesth Pain Med 2007;32:382–8. [11] Terry RL, McDonnell SM, van Eps AW, et al. Pharmacokinetic profile and behavioral effects of gabapentin in the horse. J Vet Pharmacol Ther 2010;33:485–94. [12] Guedes AG, Morisseau C, Sole A, et al. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg 2013;40:440–8. [13] Driessen B, Scandella M, Zarucco L. Development of a technique for continuous perineural blockade of the palmar nerves in the distal equine thoracic limb. Vet Anaesth Analg 2008;35:432–48. [14] Zarucco L, Driessen B, Scandella M, Cozzi F, Cantile C. Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves. Can J Vet Res 2010;74:305–13.
045 Clinical outcome of 14 obesity-associated laminitis cases managed with the same rehabilitation protocol D. Taylor 1, A. Sperandeo 2, J. Schumacher 1, T. Passler 1, A. Wooldridge 1, I. Ramey 3, and P. Ramey 3 1 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, AL, 2 Sperandeo Hoof Care, Winder, GA, 3 Hoof Rehabilitation Specialists, Inc., Lakemont, GA Take-home message: Daily exercise, dietary modification, and removing ground reaction force from the hoof wall were keys to rehabilitation for horses with obesity-associated laminitis. Introduction: A rehabilitation protocol was used to manage obese horses suffering with laminitis. and clinical outcomes were evaluated after 5–12 months of therapy. Materials and Methods: Clinical data from 14 laminitis cases were analyzed using repeated measures to evaluate
response to rehabilitation. Each horse was presented as obese and laminitic, with no history of a systemic inflammatory disease. The rehabilitation method emphasized a mineral-balanced, low- nonstructural carbohydrate diet; daily exercise; hoof trimming that minimized hoof wall loading; and sole protection in the form of rubber hoof boots and/or hoof casts. Results: The alignment of the third phalanx (P3) within the hoof capsule was significantly improved and hoof wall thickness was significantly decreased (p < 0.0001) following treatment. Sole depth was significantly increased (p < 0.0015). Reduction of palmar angle measurements was detected in acutely and chronically affected horses. This treatment effect was statistically greater for horses with chronic laminitis than for horses with acute laminitis (p < 0.0001). Horses were 5.5 times more likely to be sound post-treatment than pre-treatment. Discussion and Conclusions: Daily exercise, dietary modification, and removing ground reaction force from the hoof wall were the foci of the rehabilitation program. The hoof care and husbandry applied to these horses may be an effective method of rehabilitation for horses with obesityassociated laminitis.
046 A reproducible model for long-term rehabilitation of the foundered equine metabolic syndrome horse Daisy A. Bicking Daisy Haven Farm, Inc., Parkesburg, PA Take-home message: Success in rehabilitating the foundered EMS horse is based on a strict protocol to control laminitis triggers and by working as a team with the veterinarian and caretakers. Introduction: Equine metabolic syndrome (EMS) is one of the most common causes of laminitis. Due to diverse management issues, a comprehensive protocol is critical to successful rehabilitation. Our management protocol includes five aspects: (1) veterinary diagnosis, (2) custom, low-glycemic diet, (3) corrective trimming, (4) environmental restrictions, and (5) caretaker compliance. Materials and Methods: A retrospective study was conducted of 110 horses with laminitis secondary to EMS (presence of laminitis and hyperinsulinemia). Management success was determined by improvement of radiographic alignment, pain level, and body condition over time. A custom, low-glycemic diet was fed which used a forage that was < 13% nonstructural carbohydrates (NSC) and fed at a rate of 1.5% bwt/day. Horses were restricted to gravel paddocks. Hoof-care included trimming/shoeing with radiographic guidance. Clients were educated and provided serial digital images/radiographs of the feet. Results: The horses were followed for 1–9 years. Most (77 horses) were rehabilitated barefoot; 33 horses were shod. Most (80 horses) were managed off-site; 30 horses were managed at our rehabilitation facility. Of the 110 horses
Abstracts / Journal of Equine Veterinary Science 33 (2013) 860-883
studied, 105 horses returned to their pre-laminitic level of soundness. Discussion: Strict management of the EMS horse is critical to success. While veterinary diagnosis, strict diet, and appropriate hoof-care are key, without managing the environment and gaining the compliance of the caretaker, rehabilitation will likely be limited and temporary. Conclusion and Clinical Relevance: Success in rehabilitating the foundered EMS horse is based on a strict protocol to control laminitis triggers and by working as a team with the veterinarian and caretakers.
047 Pain-associated changes in the dorsal root ganglia of laminitic horses F. Gauff 1, 4, H. Jerina 2, 4, E. Jones 3, R. Mitchell 2, S. Fleetwood-Walker 2, and T. Licka 1, 3 1 Department of Horses and Small Animals, Vienna University of Veterinary Medicine, Austria, 2 Centre for Integrative Physiology, Sensory Neuroscience, University of Edinburgh, United Kingdom, 3 Department of Veterinary Clinical Studies, The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom, 4 These authors contributed equally to the work Take-home message: Laminitis with pedal bone rotation causes upregulation of pain markers in the associated dorsal root ganglia of the affected limbs. These changes undoubtedly contribute to the complex pain of severe laminitis. Introduction: Severe laminitic pain remains difficult to manage, as its development is still poorly understood. Recent studies showed that P2X3 receptors in the dorsal root ganglia (DRG) are part of nociceptive signaling in cancer pain. Increased concentrations of endothelin-1 (ET1) in nerve fibers of the hoof after hyperinsulinaemia have also been documented and may contribute to the pain of laminitis. In this study we investigated the expression of these and other pain markers in the DRG of laminitic horses. Materials and Methods: Dorsal root ganglia from cervical segments 8 (C8, forelimb innervation) and 4 (C4, non-forelimb innervation) were obtained postmortem from 5 laminitic horses (mean pedal bone rotation, 8.2 3.0 ; mean D-distance, 16.4 4.9 mm) and 4 control horses. Cryostatic sections were incubated with primary antibodies for pain-associated markers plus the nociceptive C-fiber marker peripherin, and visualized with ALEXA-fluor secondary antibodies for confocal imaging. Results: Compared with control samples, expression of the P2X3 receptor, ET-1, and endothelin receptor A (ETRA), but not B (ETRB), were significantly increased in peripherinpositive cells of the DRG from laminitic horses at C8, but not at C4.
871
Discussion and Conclusions: In laminitic pain, there is upregulation of the P2X3 receptor and ET-1, as well as ETRA, in the associated DRG, similar to cancer pain and complex regional pain syndrome in humans. Increased expression of ET-1 may be related to the severity of laminitic pain. Increased expression of ETRA in the DRG potentially increases nociception from increased ET-1 in the laminar tissue, as shown after intraplantar ET-1 injections in rodents; and blocking ETRA suppresses overt ET-1associated pain in a rodent model. In unrelenting, severe laminitis pain, there is a rationale for using the dual endothelin receptor antagonist, Bosentan.
048 Reparixin, an antagonist of CXCR1/2, in experimental laminitis Leonardo R. Lima 1, Heloisa M. Falcão Mendes 1, Frederico M. Soriani 2, Geraldo Eleno S. Alves 1, Danielle G. de Souza 2, Mauro M. Teixeira 2, and Rafael R. Faleiros 1 1 Department of Veterinary Clinics and Surgery, Escola de Veterinária da Universidade Federal de Minas Gerais, MG, Brazil, 2 Immunopharmacology, Department of Immunology and Biochemistry, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Take-home message: Although reparixin did not interfere with the development of clinical signs, it prevented laminar inflammation and epidermal deterioration in the treated group. Introduction: Chemokine expression and leukocyte infiltration in laminar tissue are consistent events in equine acute laminitis. The objective was to evaluate the effects of intravenous infusion of reparixin, a selective antagonist for CXCR1 and CXCR2 chemokine receptors, in horses subjected to the oligofructose (OF) laminitis model. Materials and Methods: Twelve light horses (305 35 kg) were given OF (10 g/kg PO) and divided into 2 groups: treated (reparixin, 30 mg/kg IV at 6, 12, 18, and 24 h after OF) and untreated. Clinical and hematologic variables were recorded before and 6, 12, 18, 24, 36, 48, 60, and 72 h after OF administration. Laminar biopsy samples were taken before and 12, 36, and 72 h after OF. Histological sections were stained with PAS and scored from 0 to 6 for epidermal cell and basal membrane changes. The RNA expression of IL-1b, IL-6, and CXCL1 were determined by RT-PCR. Data were subjected to ANOVA (p < 0.05). Results: Laminitis signs were mild in both groups. Reparixin treatment did not affect clinical signs or cause any apparent adverse effect. Increases from basal levels in PAS grades and in IL-1b and IL-6 RNA expressions were seen in untreated but not in treated horses. Discussion and Conclusions: Although the reparixin therapy protocol did not interfere with the development of clinical signs, it prevented laminar inflammation
Abstracts / Journal of Equine Veterinary Science 33 (2013) 860-883
References [1] van Eps AW, Pollitt CC. Equine laminitis model: lamellar histopathology seven days after induction with oligofructose. Equine Vet J 2009;41:735–40. [2] Jones E, Vinuela-Fernandez I, Eager RA, et al. Neuropathic changes in equine laminitis pain. Pain 2007;132:321–31. [3] Morgan SJ, Grosenbaugh DA, Hood DM. The pathophysiology of chronic laminitis. Pain and anatomic pathology. Vet Clin North Am Equine Pract 1999;15:395–417. [4] van Eps AW, Leise BS, Watts M, Pollitt CC, Belknap JK. Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model. Equine Vet J 2012;44:230–7. [5] Belknap JK, Giguere S, Pettigrew A, Cochran AM, van Eps AW, Pollitt CC. Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response. Equine Vet J 2007;39: 42–7. [6] Fontaine GL, Belknap JK, Allen D, Moore JN, Kroll DL. Expression of interleukin-1beta in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. Am J Vet Res 2001;62: 714–20. [7] Pollitt CC. Basement membrane pathology: a feature of acute equine laminitis. Equine Vet J 1996;28:38–46. [8] Abrahamsen EJ. How to manage acute pain in laminitis. In: Proceedings of the Congress of the British Equine Veterinary Association. Birmingham: Equine Veterinary Journal Ltd.; 2005: 195–6. [9] Harding LM, Kristensen JD, Baranowski AP. Differential effects of neuropathic analgesics on wind-up-like pain and somatosensory function in healthy volunteers. Clin J Pain 2005;21:127–32. [10] Arendt-Nielsen L, Frokjaer JB, Staahl C, et al. Effects of gabapentin on experimental somatic pain and temporal summation. Reg Anesth Pain Med 2007;32:382–8. [11] Terry RL, McDonnell SM, van Eps AW, et al. Pharmacokinetic profile and behavioral effects of gabapentin in the horse. J Vet Pharmacol Ther 2010;33:485–94. [12] Guedes AG, Morisseau C, Sole A, et al. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg 2013;40:440–8. [13] Driessen B, Scandella M, Zarucco L. Development of a technique for continuous perineural blockade of the palmar nerves in the distal equine thoracic limb. Vet Anaesth Analg 2008;35:432–48. [14] Zarucco L, Driessen B, Scandella M, Cozzi F, Cantile C. Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves. Can J Vet Res 2010;74:305–13.
045 Clinical outcome of 14 obesity-associated laminitis cases managed with the same rehabilitation protocol D. Taylor 1, A. Sperandeo 2, J. Schumacher 1, T. Passler 1, A. Wooldridge 1, I. Ramey 3, and P. Ramey 3 1 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, AL, 2 Sperandeo Hoof Care, Winder, GA, 3 Hoof Rehabilitation Specialists, Inc., Lakemont, GA Take-home message: Daily exercise, dietary modification, and removing ground reaction force from the hoof wall were keys to rehabilitation for horses with obesity-associated laminitis. Introduction: A rehabilitation protocol was used to manage obese horses suffering with laminitis. and clinical outcomes were evaluated after 5–12 months of therapy. Materials and Methods: Clinical data from 14 laminitis cases were analyzed using repeated measures to evaluate
response to rehabilitation. Each horse was presented as obese and laminitic, with no history of a systemic inflammatory disease. The rehabilitation method emphasized a mineral-balanced, low- nonstructural carbohydrate diet; daily exercise; hoof trimming that minimized hoof wall loading; and sole protection in the form of rubber hoof boots and/or hoof casts. Results: The alignment of the third phalanx (P3) within the hoof capsule was significantly improved and hoof wall thickness was significantly decreased (p < 0.0001) following treatment. Sole depth was significantly increased (p < 0.0015). Reduction of palmar angle measurements was detected in acutely and chronically affected horses. This treatment effect was statistically greater for horses with chronic laminitis than for horses with acute laminitis (p < 0.0001). Horses were 5.5 times more likely to be sound post-treatment than pre-treatment. Discussion and Conclusions: Daily exercise, dietary modification, and removing ground reaction force from the hoof wall were the foci of the rehabilitation program. The hoof care and husbandry applied to these horses may be an effective method of rehabilitation for horses with obesityassociated laminitis.
046 A reproducible model for long-term rehabilitation of the foundered equine metabolic syndrome horse Daisy A. Bicking Daisy Haven Farm, Inc., Parkesburg, PA Take-home message: Success in rehabilitating the foundered EMS horse is based on a strict protocol to control laminitis triggers and by working as a team with the veterinarian and caretakers. Introduction: Equine metabolic syndrome (EMS) is one of the most common causes of laminitis. Due to diverse management issues, a comprehensive protocol is critical to successful rehabilitation. Our management protocol includes five aspects: (1) veterinary diagnosis, (2) custom, low-glycemic diet, (3) corrective trimming, (4) environmental restrictions, and (5) caretaker compliance. Materials and Methods: A retrospective study was conducted of 110 horses with laminitis secondary to EMS (presence of laminitis and hyperinsulinemia). Management success was determined by improvement of radiographic alignment, pain level, and body condition over time. A custom, low-glycemic diet was fed which used a forage that was < 13% nonstructural carbohydrates (NSC) and fed at a rate of 1.5% bwt/day. Horses were restricted to gravel paddocks. Hoof-care included trimming/shoeing with radiographic guidance. Clients were educated and provided serial digital images/radiographs of the feet. Results: The horses were followed for 1–9 years. Most (77 horses) were rehabilitated barefoot; 33 horses were shod. Most (80 horses) were managed off-site; 30 horses were managed at our rehabilitation facility. Of the 110 horses
Abstracts / Journal of Equine Veterinary Science 33 (2013) 860-883
studied, 105 horses returned to their pre-laminitic level of soundness. Discussion: Strict management of the EMS horse is critical to success. While veterinary diagnosis, strict diet, and appropriate hoof-care are key, without managing the environment and gaining the compliance of the caretaker, rehabilitation will likely be limited and temporary. Conclusion and Clinical Relevance: Success in rehabilitating the foundered EMS horse is based on a strict protocol to control laminitis triggers and by working as a team with the veterinarian and caretakers.
047 Pain-associated changes in the dorsal root ganglia of laminitic horses F. Gauff 1, 4, H. Jerina 2, 4, E. Jones 3, R. Mitchell 2, S. Fleetwood-Walker 2, and T. Licka 1, 3 1 Department of Horses and Small Animals, Vienna University of Veterinary Medicine, Austria, 2 Centre for Integrative Physiology, Sensory Neuroscience, University of Edinburgh, United Kingdom, 3 Department of Veterinary Clinical Studies, The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom, 4 These authors contributed equally to the work Take-home message: Laminitis with pedal bone rotation causes upregulation of pain markers in the associated dorsal root ganglia of the affected limbs. These changes undoubtedly contribute to the complex pain of severe laminitis. Introduction: Severe laminitic pain remains difficult to manage, as its development is still poorly understood. Recent studies showed that P2X3 receptors in the dorsal root ganglia (DRG) are part of nociceptive signaling in cancer pain. Increased concentrations of endothelin-1 (ET1) in nerve fibers of the hoof after hyperinsulinaemia have also been documented and may contribute to the pain of laminitis. In this study we investigated the expression of these and other pain markers in the DRG of laminitic horses. Materials and Methods: Dorsal root ganglia from cervical segments 8 (C8, forelimb innervation) and 4 (C4, non-forelimb innervation) were obtained postmortem from 5 laminitic horses (mean pedal bone rotation, 8.2 3.0 ; mean D-distance, 16.4 4.9 mm) and 4 control horses. Cryostatic sections were incubated with primary antibodies for pain-associated markers plus the nociceptive C-fiber marker peripherin, and visualized with ALEXA-fluor secondary antibodies for confocal imaging. Results: Compared with control samples, expression of the P2X3 receptor, ET-1, and endothelin receptor A (ETRA), but not B (ETRB), were significantly increased in peripherinpositive cells of the DRG from laminitic horses at C8, but not at C4.
871
Discussion and Conclusions: In laminitic pain, there is upregulation of the P2X3 receptor and ET-1, as well as ETRA, in the associated DRG, similar to cancer pain and complex regional pain syndrome in humans. Increased expression of ET-1 may be related to the severity of laminitic pain. Increased expression of ETRA in the DRG potentially increases nociception from increased ET-1 in the laminar tissue, as shown after intraplantar ET-1 injections in rodents; and blocking ETRA suppresses overt ET-1associated pain in a rodent model. In unrelenting, severe laminitis pain, there is a rationale for using the dual endothelin receptor antagonist, Bosentan.
048 Reparixin, an antagonist of CXCR1/2, in experimental laminitis Leonardo R. Lima 1, Heloisa M. Falcão Mendes 1, Frederico M. Soriani 2, Geraldo Eleno S. Alves 1, Danielle G. de Souza 2, Mauro M. Teixeira 2, and Rafael R. Faleiros 1 1 Department of Veterinary Clinics and Surgery, Escola de Veterinária da Universidade Federal de Minas Gerais, MG, Brazil, 2 Immunopharmacology, Department of Immunology and Biochemistry, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Take-home message: Although reparixin did not interfere with the development of clinical signs, it prevented laminar inflammation and epidermal deterioration in the treated group. Introduction: Chemokine expression and leukocyte infiltration in laminar tissue are consistent events in equine acute laminitis. The objective was to evaluate the effects of intravenous infusion of reparixin, a selective antagonist for CXCR1 and CXCR2 chemokine receptors, in horses subjected to the oligofructose (OF) laminitis model. Materials and Methods: Twelve light horses (305 35 kg) were given OF (10 g/kg PO) and divided into 2 groups: treated (reparixin, 30 mg/kg IV at 6, 12, 18, and 24 h after OF) and untreated. Clinical and hematologic variables were recorded before and 6, 12, 18, 24, 36, 48, 60, and 72 h after OF administration. Laminar biopsy samples were taken before and 12, 36, and 72 h after OF. Histological sections were stained with PAS and scored from 0 to 6 for epidermal cell and basal membrane changes. The RNA expression of IL-1b, IL-6, and CXCL1 were determined by RT-PCR. Data were subjected to ANOVA (p < 0.05). Results: Laminitis signs were mild in both groups. Reparixin treatment did not affect clinical signs or cause any apparent adverse effect. Increases from basal levels in PAS grades and in IL-1b and IL-6 RNA expressions were seen in untreated but not in treated horses. Discussion and Conclusions: Although the reparixin therapy protocol did not interfere with the development of clinical signs, it prevented laminar inflammation