- Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT\(_{2B}\) receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT\(_{2B}\) receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice. Considering the role 5-HT\(_{2B}\) receptors play in hypoxia-induced pulmonary vessel muscularization, we were encouraged to keep mice under hypoxic conditions and tested whether this treatment will render them susceptible to mCPP-induced dural PPE. Following four-week of hypoxia, PPE, associated with increased transendothelial transport, was induced by mCPP. The effect was blocked by sumatriptan. Chronic application of 5-HT\(_{2B}\) receptor or nitric oxide synthase blockers during hypoxia prevented the development of susceptibility. Here we present a migraine model that distinguishes between a migraine-like state (hypoxic mice) and normal, normoxic mice and mimics processes that are related to chronic activation of 5-HT\(_{2B}\) receptors under hypoxia. It seems striking, that chronic endogenous activation of 5-HT\(_{2B}\) receptors is crucial for the sensitization since 5-HT\(_{2B}\) receptor antagonists have strong, albeit delayed migraine prophylactic efficacy.
MetadatenAuthor: | Anika HunfeldGND, Daniel SegelckeGND, Ingo BäckerGND, Badreddine MecheriGND, Kathrin HemmerGND, Elisabeth DlugoschGND, Michael AndriskeGND, Frank ParisGND, Xinran ZhuORCiDGND, Hermann LübbertORCiDGND |
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URN: | urn:nbn:de:hbz:294-59065 |
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DOI: | https://doi.org/10.1038/srep17845 |
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Parent Title (English): | Scientific reports |
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Subtitle (English): | a novel animal model for migraine pathophysiology |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2018/07/11 |
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Date of first Publication: | 2015/12/08 |
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Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
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Tag: | Open Access Fonds |
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Volume: | 5 |
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First Page: | 17845-1 |
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Last Page: | 17845-12 |
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Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
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Note: | Scientific reports, Bd. 5.2015, Artikelnummer 17845 |
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Institutes/Facilities: | Lehrstuhl für Tierphysiologie |
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Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie |
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open_access (DINI-Set): | open_access |
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faculties: | Fakultät für Biologie und Biotechnologie |
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Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
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