title: Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception.
abstract: The soluble epoxide hydrolase (sEH) enzyme regulates the levels of endogenous epoxygenated fatty acid (EFA) lipid metabolites by rapidly degrading these molecules. The EFAs have pleiotropic biological activities including the modulation of nociceptive signaling. Recent findings indicate that the EFAs, in particular the arachidonic acid (AA) derived epoxyeicosatrienoic acids (EETs), the docosahexaenoic acid (DHA) derived epoxydocosapentaenoic acids (EpDPEs) and eicosapentaenoic acid (EPA) derived epoxyeicosatetraenoic acids (EpETEs) are natural signaling molecules. The tight regulation of these metabolites speaks to their importance in regulating biological functions. In the past several years work on EFAs in regard to their activities in the nervous system evolved to demonstrate that these molecules are anti-inflammatory and anti-nociceptive. Here we focus on the recent advances in understanding the effects of sEH inhibition and increased EFAs on the nociceptive system and their ability to reduce pain. Evidence of their role in modulating pain signaling is given by their direct application and by inhibiting their degradation in various models of pain. Moreover, there is mounting evidence of EFAs role in the crosstalk between major nociceptive and anti-nociceptive systems which is reviewed herein. Overall the fundamental knowledge generated within the past decade indicates that orally bioavailable small molecule inhibitors of sEH may find a place in the treatment of a number of diverse painful conditions including inflammatory and neuropathic pain.
authors.affiliation: Department of Entomology and UC Davis Cancer Center, University of California Davis, Davis, CA 95616, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Wagner
authors.forename: Bora
authors.initials: B
authors.lastname: Inceoglu
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D015118:Eicosapentaenoic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid