title: Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.
abstract: Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs). However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs) as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP) genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Sisignano
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Angioni
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreiros
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Schuh
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Suo
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schreiber
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Dawes
authors.affiliation: Wolfson CARD, King's College London, Guy's Campus, London, United Kindgom.
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes-Martins
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennett
authors.affiliation: Wolfson CARD, King's College London, Guy's Campus, London, United Kindgom.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Institute of Clinical Pharmacology, pharmazentrum Frankfurt/ZAFES, University Hospital of the Goethe-University, Frankfurt am Main, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Scholich
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000528:radiation effects; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology*; D019787:Linoleic Acid / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D051381:Rats; D050916:TRPV Cation Channels / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D008246:Lysophospholipids; D050916:TRPV Cation Channels; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D019787:Linoleic Acid; C032881:lysophosphatidic acid