| First Author | Zimmer B | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1863 |
| Issue | 7 | Pages | 669-678 |
| PubMed ID | 29625231 | Mgi Jnum | J:265863 |
| Mgi Id | MGI:6199787 | Doi | 10.1016/j.bbalip.2018.03.012 |
| Citation | Zimmer B, et al. (2018) The oxidized linoleic acid metabolite 12,13-DiHOME mediates thermal hyperalgesia during inflammatory pain. Biochim Biophys Acta Mol Cell Biol Lipids 1863(7):669-678 |
| abstractText | Eicosanoids play a crucial role in inflammatory pain. However, there is very little knowledge about the contribution of oxidized linoleic acid metabolites in inflammatory pain and peripheral sensitization. Here, we identify 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), a cytochrome P450-derived linoleic acid metabolite, as crucial mediator of thermal hyperalgesia during inflammatory pain. We found 12,13-DiHOME in increased concentrations in peripheral nervous tissue during acute zymosan- and complete Freund's Adjuvant-induced inflammatory pain. 12,13-DiHOME causes calcium transients in sensory neurons and sensitizes the transient receptor potential vanilloid 1 (TRPV1)-mediated intracellular calcium increases via protein kinase C, subsequently leading to enhanced TRPV1-dependent CGRP-release from sensory neurons. Peripheral injection of 12,13-DiHOME in vivo causes TRPV1-dependent thermal pain hypersensitivity. Finally, application of the soluble epoxide hydrolase (sEH)-inhibitor TPPU reduces 12,13-DiHOME concentrations in nervous tissue and reduces zymosan- and CFA-induced thermal hyperalgesia in vivo. In conclusion, we identify a novel role for the lipid mediator 12,13-DiHOME in mediating thermal hyperalgesia during inflammatory pain and propose a novel mechanism that may explain the antihyperalgesic effects of sEH inhibitors in vivo. |
