Structurally different sEHIs inhibit sEH and stabilize EFAs, and this is strongly anti-hyperalgesic and anti-allodynic. However it was not entirely clear if these effects were mediated by a non-specific interaction of the sEHIs scaffold with another target or by the EFAs themselves. Therefore we asked if the direct administration of EFAs is anti-hyperalgesic in reducing nociceptive behavior. In the LPS induced inflammatory pain model methyl esters of EETs administered topically to the site of inflammation display significant anti-hyperalgesic effects [34]. Similarly, in the carrageenan model, EETs and other EFAs reduce pain related behavior following local intraplantar injection. These effects occur at doses as low as 300ng per administration. Moreover individual regioisomers of DHA epoxides display differing anti-allodynic effects indicating the selectivity of the bioactive lipids. The differences in the ability of regioisomers to elicit anti-nociception may be related to their non-uniform presence in tissues or their ability to engage a receptor molecule [28]. However, these effects have a rapid onset beginning within 15 minutes following administration when first measurements were taken. Because sEH was not inhibited in these studies, the
