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Veterinary anaesthesia and analgesia2013; 40(4); 440-448; doi: 10.1111/vaa.12030

Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis.

Abstract: 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.
© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
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Publication Date: 2013-03-07 PubMed ID: 23463912PubMed Central: PMC3956586DOI: 10.1111/vaa.12030Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper investigates the effects of an experimental drug (t-TUCB), a soluble epoxide hydrolase (sEH) inhibitor, in managing pain in a horse suffering from laminitis and cellulitis. The study reports significant improvements in pain scores with no observable side effects.

Research Description

The study focuses on a four-year-old, Thoroughbred female horse weighing 500 kg. The horse had been diagnosed with bilateral forelimb laminitis and cellulitis on its left forelimb, leading to severe pain. Despite administering non-steroidal anti-inflammatory therapy (flunixin meglumine on days 1, 2, 3, and 4, and phenylbutazone on days 5, 6, and 7) either on its own or in combination with gabapentin (days 6 and 7), the horse’s condition did not improve. The horse’s pain scores only increased, as assessed by three separate individuals using a visual analog scale (VAS), moving from 8.5 on day 6 to 9.5 on day 7.

Research Methodology

  • As the horse’s situation deteriorated, researchers decided to introduce an experimental new drug, trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), a sEH inhibitor, to the treatment protocol.
  • The dose and frequency of administration were determined based on the drug’s potency against equine sEH to produce plasma concentrations within the range of 30 nmol L(-1) and 2.5 μmol L(-1).
  • Non-invasive blood pressure monitoring documented severe hypertension pre-treatment. The horse’s pain scores and blood pressure were tracked daily.

Results

  • Following the administration of t-TUCB, the horse’s pain scores significantly reduced and its blood pressure decreased to normal levels. The daily plasma concentrations of t-TUCB were within the expected range, while levels of phenylbutazone and gabapentin were below the efficacious concentrations.
  • No adverse side effects from t-TUCB were observed during clinical or laboratory exams. More than 120 days after treatment, no new episodes of laminitis were recorded.

Conclusions

The introduction of t-TUCB as an additive treatment greatly improved the horse’s condition. The sEH inhibitor noticeably reduced pain and normalized blood pressure in the horse. Furthermore, there were no notable negative side effects of the drug. This study suggests the need for future studies to further investigate the analgesic and protective effects of such compounds in treating painful inflammatory diseases in animals.

Cite This Article

APA
Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD. (2013). Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg, 40(4), 440-448. https://doi.org/10.1111/vaa.12030

Publication

Veterinary anaesthesia and analgesia
ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 40
Issue: 4
Pages: 440-448

Researcher Affiliations

Guedes, Alonso G P
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. aguedes@ucdavis.edu
Morisseau, Christophe
    Sole, Albert
      Soares, Joao H N
        Ulu, Arzu
          Dong, Hua
            Hammock, Bruce D

              MeSH Terms

              • Analgesics / administration & dosage
              • Analgesics / pharmacology
              • Animals
              • Benzoates / therapeutic use
              • Epoxide Hydrolases / antagonists & inhibitors
              • Female
              • Foot Diseases / drug therapy
              • Foot Diseases / veterinary
              • Hoof and Claw
              • Horse Diseases / drug therapy
              • Horses
              • Inflammation / drug therapy
              • Inflammation / veterinary
              • Pain / drug therapy
              • Phenylurea Compounds / therapeutic use

              Grant Funding

              • ES02710 / NIEHS NIH HHS
              • R01 ES002710 / NIEHS NIH HHS
              • P42 ES004699 / NIEHS NIH HHS
              • P42 ES04699 / NIEHS NIH HHS
              • R37 ES002710 / NIEHS NIH HHS

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