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 cascade has great potential for treating neuropathic pain, exploring the crosstalk between the branches of the cascade and the synergistic response it offers in pain relief may yield still more novel therapeutics. It will be interesting to describe the activity of EFAs in modulating nociception mediated through the opioid and cannabinoid analgesic systems. This crosstalk between analgesic systems offers even more opportunities to improve pain therapies by potentially lowering side effects of current agents with combination therapy. Reducing pain is still an unmet need in numerous disease states and novel alternatives to current therapies with more preferable side effect profiles are necessary. The sEH inhibition mediated anti-nociception, though yet to be tested in man, offers a unique path towards this end.
