In support of our work on inflammatory models of pain and analgesic effects of EFAs in non-inflammatory models, recent data from Terashvili et al. corroborate direct anti-nociceptive roles of EFAs, specifically EETs [65]. These studies demonstrated that site specific administration of EETs into the ventrolateral periaqueductal gray of the brain led to elevation of the thermal tail flick latency in rats and that these anti-nociceptive effects were highly correlated with an increase in the release of endogenous opioid peptides. The analgesia produced by EETs was antagonized by both β-endorphin and met-enkephalin antisera. In accordance with these results more recent work from Conroy et al. suggests that the cytochrome P450 products directly contribute to the action of opioid agonists [66]. These authors elegantly demonstrated that both inhibition of cytochrome P450s or genetic knock out of cytochrome reductase in the brain, which essentially reduces all cytochrome P450 activity, interfere with bulbospinal analgesia mediated by opioid agonists [66, 67]. The mechanism of action of these findings is still under investigation but is hypothesized to take place via P450 inhibition modulating a pathway that
