Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation

Abstract Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidon...

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Autores principales: Beatrice Oehler, Katrin Kistner, Corinna Martin, Jürgen Schiller, Rafaela Mayer, Milad Mohammadi, Reine-Solange Sauer, Milos R. Filipovic, Francisco R. Nieto, Jan Kloka, Diana Pflücke, Kerstin Hill, Michael Schaefer, Marzia Malcangio, Peter W. Reeh, Alexander Brack, Robert Blum, Heike L. Rittner
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:a6c20966bd864799baf52d5a980c648e2021-12-02T15:04:52ZInflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation10.1038/s41598-017-05348-32045-2322https://doaj.org/article/a6c20966bd864799baf52d5a980c648e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05348-3https://doaj.org/toc/2045-2322Abstract Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.Beatrice OehlerKatrin KistnerCorinna MartinJürgen SchillerRafaela MayerMilad MohammadiReine-Solange SauerMilos R. FilipovicFrancisco R. NietoJan KlokaDiana PflückeKerstin HillMichael SchaeferMarzia MalcangioPeter W. ReehAlexander BrackRobert BlumHeike L. RittnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-22 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Beatrice Oehler
Katrin Kistner
Corinna Martin
Jürgen Schiller
Rafaela Mayer
Milad Mohammadi
Reine-Solange Sauer
Milos R. Filipovic
Francisco R. Nieto
Jan Kloka
Diana Pflücke
Kerstin Hill
Michael Schaefer
Marzia Malcangio
Peter W. Reeh
Alexander Brack
Robert Blum
Heike L. Rittner
Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
description Abstract Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.
format article
author Beatrice Oehler
Katrin Kistner
Corinna Martin
Jürgen Schiller
Rafaela Mayer
Milad Mohammadi
Reine-Solange Sauer
Milos R. Filipovic
Francisco R. Nieto
Jan Kloka
Diana Pflücke
Kerstin Hill
Michael Schaefer
Marzia Malcangio
Peter W. Reeh
Alexander Brack
Robert Blum
Heike L. Rittner
author_facet Beatrice Oehler
Katrin Kistner
Corinna Martin
Jürgen Schiller
Rafaela Mayer
Milad Mohammadi
Reine-Solange Sauer
Milos R. Filipovic
Francisco R. Nieto
Jan Kloka
Diana Pflücke
Kerstin Hill
Michael Schaefer
Marzia Malcangio
Peter W. Reeh
Alexander Brack
Robert Blum
Heike L. Rittner
author_sort Beatrice Oehler
title Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
title_short Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
title_full Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
title_fullStr Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
title_full_unstemmed Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
title_sort inflammatory pain control by blocking oxidized phospholipid-mediated trp channel activation
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/a6c20966bd864799baf52d5a980c648e
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