TY  - JOUR
A1  - Oehler, Beatrice
A1  - Kloka, Jan
A1  - Mohammadi, Milad
A1  - Ben-Kraiem, Adel
A1  - Rittner, Heike L.
T1  - D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation
JF  - Molecular Pain
N2  - Background
High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model.

Results
Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F.

Conclusions
D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.
KW  - TRPA1
KW  - capsaicin
KW  - reactive oxygen species
KW  - oxidised lipids
KW  - pain
KW  - targeting
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236061
VL  - 16
ER  - 
TY  - JOUR
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.
T1  - Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
JF  - Scientific Reports
N2  - 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.
KW  - chronic pain
KW  - ion channels in the nervous system
KW  - molecular medicine
KW  - pain
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158536
VL  - 7
IS  - 5447
ER  -