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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-158536
  • 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 massPhospholipids 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.show moreshow less

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Author: Beatrice Oehler, Katrin Kistner, Corinna Martin, Jürgen Schiller, Rafaela Mayer, Milad MohammadiORCiD, 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
URN:urn:nbn:de:bvb:20-opus-158536
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Neurobiologie
Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2017
Volume:7
Issue:5447
Source:Scientific Reports 7:5447 (2017). DOI: : 10.1038/s41598-017-05348-3
DOI:https://doi.org/10.1038/s41598-017-05348-3
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:chronic pain; ion channels in the nervous system; molecular medicine; pain
Release Date:2018/03/23
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2017
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International