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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Nature Portfolio
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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) |
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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 |
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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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