Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Oehler, Beatrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloka, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohammadi, Milad UNSPECIFIED UNSPECIFIED UNSPECIFIED Ben-Kraiem, Adel UNSPECIFIED UNSPECIFIED UNSPECIFIED Rittner, Heike L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language RECEPTOR POTENTIAL A1; MAST-CELLS; SENSORY NEURONS; ACTIVATION; TRPA1; PAIN; TRPV1; CONTRIBUTES; CHOLESTEROL; MODULATION Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35184