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

Alonso G P Guedes, Christophe Morisseau, Albert Sole, Joao H N Soares, Arzu Ulu, Hua Dong, Bruce D. Hammock

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

History: 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). Physical examination: 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. Management: 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. Follow up: 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.

Original languageEnglish (US)
Pages (from-to)440-448
Number of pages9
JournalVeterinary Anaesthesia and Analgesia
Volume40
Issue number4
DOIs
StatePublished - Jul 2013

Fingerprint

epoxide hydrolase
Epoxide Hydrolases
laminitis
analgesics
Horses
Analgesics
pain
horses
Pain
phenylbutazone
Phenylbutazone
Forelimb
forelimbs
blood pressure
adverse effects
Blood Pressure
cellulitis
flunixin
Intractable Pain
therapeutics

Keywords

  • Analgesia
  • Antinociception
  • Arterial blood pressure
  • Equine
  • Nociception
  • Pain management

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Guedes, A. G. P., Morisseau, C., Sole, A., Soares, J. H. N., Ulu, A., Dong, H., & Hammock, B. D. (2013). Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Veterinary Anaesthesia and Analgesia, 40(4), 440-448. https://doi.org/10.1111/vaa.12030

Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. / Guedes, Alonso G P; Morisseau, Christophe; Sole, Albert; Soares, Joao H N; Ulu, Arzu; Dong, Hua; Hammock, Bruce D.

In: Veterinary Anaesthesia and Analgesia, Vol. 40, No. 4, 07.2013, p. 440-448.

Research output: Contribution to journalArticle

Guedes, AGP, Morisseau, C, Sole, A, Soares, JHN, Ulu, A, Dong, H & Hammock, BD 2013, 'Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis', Veterinary Anaesthesia and Analgesia, vol. 40, no. 4, pp. 440-448. https://doi.org/10.1111/vaa.12030
Guedes, Alonso G P ; Morisseau, Christophe ; Sole, Albert ; Soares, Joao H N ; Ulu, Arzu ; Dong, Hua ; Hammock, Bruce D. / Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. In: Veterinary Anaesthesia and Analgesia. 2013 ; Vol. 40, No. 4. pp. 440-448.
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abstract = "History: 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). Physical examination: 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. Management: 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. Follow up: 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.",
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