Gowler PRW, Turnbull J, Shahtaheri M, et al. - Soluble epoxide hydrolase (sEH) plays a role in chronic joint pain associated with osteoarthritis (OA), and sEH inhibition and protection of endogenous epoxyeicosatrienoic acids (EETs) from catabolism affords a potential new treatment target for OA pain.

• This study included people with chronic knee pain due to OA as well as a surgically-induced murine model of OA, to determine if sEH driven metabolism of the EETs to dihydroxyeicosatrienoic acids (DHETs) plays a critical role in chronic joint pain associated with OA and offers a new treatment target.

• In patients experiencing chronic knee pain, association of 3 pain measures with single nucleotide polymorphisms of the sEH gene, EPHX2, was identified.

• Also, circulating levels of EETs and DHETs were linked with 3 pain measures in two separate cohorts.

• TPPU {N-[1-(1-oxopropy)-4-piperidinyl]-N’-(trifluoromethoxy)phenyl]urea} given systemically both acutely and chronically reversed established pain behaviors as well as reduced circulating levels of 8,9-DHET and 14,15-DHET, in the murine OA model.

• TPPU administration had no impact on the levels of the EETs.