Taken as a whole, EFAs whether exogenously applied or increased endogenously attenuate pain related behavior. The past decade has seen a number of rapid developments in this area including the availability of orally active potent small molecule inhibitors of the sEH. EFAs are tightly regulated via reincorporation in to membranes and enzymatic degradation. In animal models they clearly attenuate inflammation and inflammatory pain but also pain not dependent on inflammation. This anti-nociception mediated by EFAs is dissimilar to that produced by most other class of therapeutics. The EFAs do not alter motor skills like analgesics and cannabinoids. They are active in inflammatory models but also in diabetic neuropathic pain and importantly other types of pain such as that produced by PGE2 that is recalcitrant to NSAIDs and steroids. The side effects profile of sEHIs is unknown, but based on data from rodent pain studies, the sEHIs seem to be highly effective. The sEHIs reduce pro-inflammatory mediators through several different mechanisms but do so without inhibiting COX or LOX enzymes and thus maintain homeostasis. While targeting the sEH in the AA
