In the CNS, key parent PUFAs are available at high concentrations, the P450s that generate EFAs, and the sEH that degrades them are selectively expressed in the glial and neuronal cells. This demonstrates the capacity for de novo synthesis, action on neuronal cells and rapid degradation via sEH [24, 25, 32, 33]. In parallel to genetic knockout in mice, chemical inhibition of sEH in rodents using potent urea inhibitors (sEHIs) stabilizes the EETs and other EFAs in vivo leading to significant increases in their plasma and tissue levels and often decreases the corresponding diols. Extensive use of sEHIs in the past 5 years has allowed observation of numerous biological functions of EFAs, most prominently their anti-nociceptive effects [34]. Interestingly we recently found that neuronal sEH expression shows a bias towards axonal regions as opposed to dendrites [35]. If the presynaptic degradation of EFAs is more efficient than post synaptic degradation this may indicate a more prominent postsynaptic function.
