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Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception.
Prostaglandins Other Lipid Mediat. 2011 Nov; 96(1-4):76-83.PO

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+Show Affiliations

Department of Entomology and UC Davis Cancer Center, University of California Davis, Davis, CA 95616, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21854866

Citation

Wagner, Karen, et al. "Soluble Epoxide Hydrolase Inhibition, Epoxygenated Fatty Acids and Nociception." Prostaglandins & Other Lipid Mediators, vol. 96, no. 1-4, 2011, pp. 76-83.
Wagner K, Inceoglu B, Hammock BD. Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception. Prostaglandins Other Lipid Mediat. 2011;96(1-4):76-83.
Wagner, K., Inceoglu, B., & Hammock, B. D. (2011). Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception. Prostaglandins & Other Lipid Mediators, 96(1-4), 76-83. https://doi.org/10.1016/j.prostaglandins.2011.08.001
Wagner K, Inceoglu B, Hammock BD. Soluble Epoxide Hydrolase Inhibition, Epoxygenated Fatty Acids and Nociception. Prostaglandins Other Lipid Mediat. 2011;96(1-4):76-83. PubMed PMID: 21854866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception. AU - Wagner,Karen, AU - Inceoglu,Bora, AU - Hammock,Bruce D, Y1 - 2011/08/10/ PY - 2011/05/02/received PY - 2011/06/28/revised PY - 2011/08/02/accepted PY - 2011/8/23/entrez PY - 2011/8/23/pubmed PY - 2012/4/18/medline SP - 76 EP - 83 JF - Prostaglandins & other lipid mediators JO - Prostaglandins Other Lipid Mediat. VL - 96 IS - 1-4 N2 - 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. SN - 1098-8823 UR - https://www.unboundmedicine.com/medline/citation/21854866/Soluble_epoxide_hydrolase_inhibition_epoxygenated_fatty_acids_and_nociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1098-8823(11)00071-2 DB - PRIME DP - Unbound Medicine ER -