Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.
Authors: Guedes A, Galuppo L, Hood D, Hwang S H, Morisseau C, Hammock B D
Journal: Equine veterinary journal
Summary
# Soluble epoxide hydrolase inhibition in chronic equine laminitis Soluble epoxide hydrolase (sEH) regulates lipid mediators implicated in both inflammatory and neuropathic pain pathways, making it a plausible therapeutic target for improving analgesia in laminitis cases. Guedes and colleagues measured sEH activity in digital laminae tissue from healthy and laminitic horses post-mortem, then screened seven synthetic inhibitors in vitro before trialling one compound (t-TUCB) as adjunctive pain therapy in ten chronically laminitic horses (mostly Obel grades 3–4), recording daily forelimb lifts and pain scores alongside standard clinical monitoring over approximately four days of treatment. Digital laminae from laminitic horses exhibited significantly elevated sEH activity—approximately 5.3 times higher than in healthy tissues (0.9 versus 0.17 nmol/min/mg)—supporting a pathophysiological role for this enzyme in laminitis pain. Treatment with t-TUCB resulted in meaningful reductions: forelimb lifts decreased by 36% and pain scores by 18% compared with baseline, though the uncontrolled case series design and brief treatment window (limited by case attrition to 4.3 days mean duration) prevent firm conclusions about efficacy or optimal dosing protocols. Whilst two adverse events occurred during the trial, the biochemical evidence of elevated sEH activity in laminitic tissue and the analgesic signal warrant further investigation of sEH inhibitors as adjuncts in chronic laminitis management, particularly within controlled, blinded studies designed to establish safety and practical utility for practitioners.
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Practical Takeaways
- •sEH inhibition may offer a novel pharmacologic approach to managing pain in chronic laminitis cases by targeting lipid-mediated inflammatory pathways
- •t-TUCB showed modest but measurable improvements in lameness signs and pain scores when used as adjunct therapy, though treatment duration was short and adverse effects occurred
- •This preliminary work supports further controlled investigation of sEH inhibitors in laminitis management, but clinical utility remains unproven without randomized controlled trials
Key Findings
- •sEH activity in digital laminae of laminitic horses (0.9±0.6 nmol/min/mg) was significantly higher than in healthy horses (0.17±0.09 nmol/min/mg; P=0.01)
- •t-TUCB sEH inhibitor treatment for up to 10 days resulted in 36±22% reduction in forelimb lifts and 18±23% reduction in pain scores compared to baseline (P=0.04)
- •One horse developed gas colic and another corneal vascularisation during t-TUCB treatment
- •Seven synthetic sEH inhibitors were screened in vitro using equine liver cytosol, with t-TUCB selected based on potency and stability