title: Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.
abstract: BACKGROUND
  The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  In vitro experiments and clinical case series.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Absence of control group and evaluator blinding in case series.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, USA.|Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: A
authors.initials: A
authors.lastname: Guedes
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: L
authors.initials: L
authors.lastname: Galuppo
authors.affiliation: The Hoof Diagnostic and Rehabilitation Clinic, Bryan, Texas, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hood
authors.affiliation: Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.
authors.forename: C
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005534:Foot Diseases / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D006724:Hoof and Claw / Q000473:pathology*; D006734:Horse Diseases / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006736:Horses; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D008099:Liver / Q000201:enzymology; D008297:Male; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C572961:4-(4-(3-(4-trifluoromethoxy-phenyl)ureido)cyclohexyloxy)benzoic acid; D001565:Benzoates; D010671:Phenylurea Compounds; D004851:Epoxide Hydrolases
keywords: fatty acid; hoof; horse; hyperalgesia; lameness; neuropathic pain