Pharmaceutical Effects of Inhibiting the Soluble Epoxide Hydrolase in Canine Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease that causes pain and bone deterioration driven by an increase in prostaglandins and inflammatory cytokines. Current treatments focus on inhibiting prostaglandin production, a pro-inflammatory lipid metabolite, with NSAID drugs; however, other lipid signaling targets could provide safer and more effective treatment strategies. Epoxides of polyunsaturated fatty acids are anti-inflammatory lipid mediators that are rapidly metabolized by the soluble epoxide hydrolase (sEH) into corresponding vicinal diols. sEH inhibitors (sEHI) stabilize these biologically active, anti-inflammatory lipid epoxides and are analgesic in both neuropathic and inflammatory pain conditions. Additionally, increased diols have been observed in the synovial fluid of humans with OA, warranting further research on the biological role of this pathway in the progression of OA.

Most experimental studies testing the analgesic effects of sEH inhibitors have used experim...