Oehler, Beatrice, Kloka, Jan, Mohammadi, Milad, Ben-Kraiem, Adel and Rittner, Heike L. (2020). D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation. Mol. Pain, 16. THOUSAND OAKS: SAGE PUBLICATIONS INC. ISSN 1744-8069
Full text not available from this repository.Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-351845 | ||||||||||||||||||||||||
DOI: | 10.1177/1744806920903848 | ||||||||||||||||||||||||
Journal or Publication Title: | Mol. Pain | ||||||||||||||||||||||||
Volume: | 16 | ||||||||||||||||||||||||
Date: | 2020 | ||||||||||||||||||||||||
Publisher: | SAGE PUBLICATIONS INC | ||||||||||||||||||||||||
Place of Publication: | THOUSAND OAKS | ||||||||||||||||||||||||
ISSN: | 1744-8069 | ||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/35184 |
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