Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis

• Published in: Equine veterinary journal Vol. 49; no. 3; p. 345
• Main Authors: Guedes, A, Galuppo, L, Hood, D, Hwang, S H, Morisseau, C, Hammock, B D
• Format: Journal Article
• Language: English
• Published: United States 01.05.2017
• Subjects: Animals; Benzoates - chemistry; Benzoates - pharmacology; Benzoates - therapeutic use; Chronic Disease; Epoxide Hydrolases - antagonists & inhibitors; Epoxide Hydrolases - genetics; Epoxide Hydrolases - metabolism; Female; Foot Diseases - drug therapy; Foot Diseases - enzymology; Foot Diseases - veterinary; Hoof and Claw - pathology; Horse Diseases - enzymology; Horse Diseases - metabolism; Horse Diseases - pathology; Horses; Inflammation - drug therapy; Inflammation - enzymology; Inflammation - veterinary; Liver - enzymology; Male; Molecular Structure; Phenylurea Compounds - chemistry; Phenylurea Compounds - pharmacology; Phenylurea Compounds - therapeutic use; horse; fatty acid; neuropathic pain; lameness; hyperalgesia; hoof
• ISSN: 2042-3306
• DOI: 10.1111/evj.12603

The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. To determine soluble epoxide hydrolase (sEH) activity in the digital laminae, sEH inhibitor potency in vitro, and efficacy of a sEH inhibitor as an adjunct analgesic therapy in chronic laminitic horses. In vitro experiments and clinical case series. sEH activity was measured in digital laminae from euthanised healthy and laminitic horses (n = 5-6/group). Potency of 7 synthetic sEH inhibitors was determined in vitro using equine liver cytosol. One of them (t-TUCB; 0.1 mg/kg bwt i.v. every 24 h) was selected based on potency and stability, and used as adjunct therapy in 10 horses with severe chronic laminitis (Obel grades 2, one horse; 3-4, nine horses). Daily assessments of forelimb lifts, pain scores, physiologic and laboratory examinations were performed before (baseline) and during t-TUCB treatment. Data are presented as mean ± s.d. and 95% confidence intervals (CI). sEH activity in the digital laminae from laminitic horses (0.9±0.6 nmol/min/mg; 95% CI 0.16-1.55 nmol/min/mg) was significantly greater (P = 0.01) than in healthy horses (0.17±0.09 nmol/min/mg; CI 0.07-0.26 nmol/min/mg). t-TUCB as an adjunct analgesic up to 10 days (4.3±3 days) in laminitic horses was associated with significant reduction in forelimb lifts (36±22%; 95% CI 9-64%) and in pain scores (18±23%; 95% CI 2-35%) compared with baseline (P = 0.04). One horse developed gas colic and another corneal vascularisation in a blind eye during treatment. No other significant changes were observed. Absence of control group and evaluator blinding in case series. sEH activity is significantly higher in the digital laminae of actively laminitic compared with healthy horses, and use of a potent inhibitor of equine sEH as adjunct analgesic therapy appears to decrease signs of pathologic pain in laminitic horses.