D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation
- 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.
Author: | Beatrice Oehler, Jan Andreas KlokaORCiDGND, Milad Mohammadi, Adel Ben-Kraiem, Heike Rittner |
---|---|
URN: | urn:nbn:de:hebis:30:3-529731 |
DOI: | https://doi.org/10.1177/1744806920903848 |
ISSN: | 1744-8069 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31996074 |
Parent Title (English): | Molecular pain |
Publisher: | Sage |
Place of publication: | London |
Document Type: | Article |
Language: | English |
Year of Completion: | 2020 |
Date of first Publication: | 2020/01/29 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/03/02 |
Tag: | TRPA1; capsaicin; oxidised lipids; pain; reactive oxygen species; targeting |
Volume: | 16 |
Page Number: | 11 |
First Page: | 1 |
Last Page: | 11 |
Note: | Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
HeBIS-PPN: | 46142357X |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |