RT Journal Article
T1 Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation.
A1 Oehler, Beatrice
A1 Kistner, Katrin
A1 Martin, Corinna
A1 Schiller, Jürgen
A1 Mayer, Rafaela
A1 Mohammadi, Milad
A1 Sauer, Reine-Solange
A1 Filipovic, Milos R
A1 Nieto, Francisco R
A1 Kloka, Jan
A1 Pflücke, Diana
A1 Hill, Kerstin
A1 Schaefer, Michael
A1 Malcangio, Marzia
A1 Reeh, Peter W
A1 Brack, Alexander
A1 Blum, Robert
A1 Rittner, Heike L
AB 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.
YR 2017
FD 2017-07-14
LK http://hdl.handle.net/10668/11409
UL http://hdl.handle.net/10668/11409
LA en
DS RISalud
RD Apr 7, 2025