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

A. Guedes, Larry D Galuppo, D. Hood, S. H. Hwang, C. Morisseau, B. D. Hammock

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. Objectives: 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. Study design: 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. Main limitations: 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.

Original languageEnglish (US)
JournalEquine Veterinary Journal
DOIs
StateAccepted/In press - 2016

Fingerprint

epoxide hydrolase
Epoxide Hydrolases
laminitis
Horses
horses
laminae (animals)
pain
confidence interval
Confidence Intervals
analgesics
Analgesics
Forelimb
forelimbs
Pain
Inhibition (Psychology)
therapeutics
Therapeutics
Colic
colic
Neuralgia

Keywords

  • Fatty acid
  • Hoof
  • Horse
  • Hyperalgesia
  • Lameness
  • Neuropathic pain

ASJC Scopus subject areas

  • Equine

Cite this

Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis. / Guedes, A.; Galuppo, Larry D; Hood, D.; Hwang, S. H.; Morisseau, C.; Hammock, B. D.

In: Equine Veterinary Journal, 2016.

Research output: Contribution to journalArticle

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abstract = "Background: The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. Objectives: 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. Study design: 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. Main limitations: 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.",
keywords = "Fatty acid, Hoof, Horse, Hyperalgesia, Lameness, Neuropathic pain",
author = "A. Guedes and Galuppo, {Larry D} and D. Hood and Hwang, {S. H.} and C. Morisseau and Hammock, {B. D.}",
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AU - Guedes, A.

AU - Galuppo, Larry D

AU - Hood, D.

AU - Hwang, S. H.

AU - Morisseau, C.

AU - Hammock, B. D.

PY - 2016

Y1 - 2016

N2 - Background: The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. Objectives: 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. Study design: 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. Main limitations: 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.

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KW - Fatty acid

KW - Hoof

KW - Horse

KW - Hyperalgesia

KW - Lameness

KW - Neuropathic pain

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