title: Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis.
abstract: METHODS
  A 4-year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non-steroidal anti-inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7).
  
  
  METHODS
  Pain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non-invasive blood pressure monitoring revealed severe hypertension.
  
  
  RESULTS
  As euthanasia was being considered for humane reasons, a decision was made to add an experimental new drug, trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), which is a soluble epoxide hydrolase (sEH) inhibitor, to the treatment protocol. Dose and frequency of administration were selected based on the drug potency against equine sEH to produce plasma concentrations within the range of 30 nmol L(-1) and 2.5 μmol L(-1) . Pain scores decreased sharply and remarkably following t-TUCB administration and blood pressure progressively decreased to physiologic normal values. Plasma concentrations of t-TUCB, measured daily, were within the expected range, whereas phenylbutazone and gabapentin plasma levels were below the suggested efficacious concentrations.
  
  
  RESULTS
  No adverse effects were detected on clinical and laboratory examinations during and after t-TUCB administration. No new episodes of laminitis have been noted up to the time of writing (120 days following treatment).
  
  
  CONCLUSIONS
  Inhibition of sEH with t-TUCB was associated with a significant improvement in pain scores in one horse with laminitis whose pain was refractory to the standard of care therapy. No adverse effects were noticed. Future studies evaluating the analgesic and protective effects of these compounds in painful inflammatory diseases in animals are warranted.
authors: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. aguedes@ucdavis.edu
authors: Alonso G P
authors: AG
authors: Guedes
authors: Christophe
authors: C
authors: Morisseau
authors: Albert
authors: A
authors: Sole
authors: Joao H N
authors: JH
authors: Soares
authors: Arzu
authors: A
authors: Ulu
authors: Hua
authors: H
authors: Dong
authors: Bruce D
authors: BD
authors: Hammock
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005260:Female; D005534:Foot Diseases / Q000188:drug therapy / Q000662:veterinary*; D006724:Hoof and Claw; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary*; D010146:Pain / Q000188:drug therapy; D010671:Phenylurea Compounds / Q000627:therapeutic use*
chemical_list: C572961:4-(4-(3-(4-trifluoromethoxy-phenyl)ureido)cyclohexyloxy)benzoic acid; D000700:Analgesics; D001565:Benzoates; D010671:Phenylurea Compounds; D004851:Epoxide Hydrolases