With the availability of potent sEHIs the first in vivo tests of stabilizing EETs proved to be strongly anti-inflammatory in a murine model of sepsis elicited by a high dose of LPS [54]. These initial experiments indicated a prominent mechanism of sEHI mediated anti-inflammation was a sharp reduction of levels of prostanoids, importantly PGE2. As a result we asked if inhibition of sEH would decrease inflammatory pain [55]. Consistent with the LPS induced sepsis model we used an LPS induced inflammatory pain model, which is more reflective of an infection mediated pain. Intraplantar administration of LPS to the hind paw elicits both allodynia, sensitivity to innocuous stimulation, and hyperalgesia, enhanced sensitivity to normally noxious stimuli [56]. These changes in responses are thought to be mediated by sensitization of nociceptive neurons to stimuli by a number of pro-inflammatory mediators including eicosanoids. A number of structurally different sEHIs attenuate both allodynia and thermal hyperalgesia under these conditions and the anti-nociceptive effects are highly correlated with increases in EFAs brought about by sEH inhibition [34]. These effects are dose dependent and are comparable
