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EHMTI-0093. Investigation of 5-HT2B receptor pathways with relevance to a mouse migraine model

Introduction

Recent research raises the question whether the serotonin 2B receptor (5-HT2B) plays a role in the pathogenesis of migraine. Clinical studies revealed that the 5-HT2B/2C agonist meta-Chlorophenylpiperazine (mCPP) induces migraine-like headache more likely in migraineurs than in subjects without a history of migraine. We therefore developed an animal model for chronic migraine, where we are able to induce a neurogenic inflammation in the dura mater of hypoxic mice with 5-HT2B agonists. This inflammation can be blocked by specific 5-HT2B inhibitors.

Until now little is known about the 5-HT2B receptor: It is expressed on endothelial cells of blood vessels, but it may also be present on other cell types. Like most of the other serotonin receptors it is a G protein-coupled receptor, but the native signal transduction pathway after receptor activation is not clear yet.

Aims

Investigation of the 5-HT2B receptor in a primary cell culture system to determine native signal transduction pathways.

Methods

Cultivation of primary cells. Validation of the presence of the receptor. Signal transduction assays.

Results

Stimulation with the 5-HT2B/2C agonist mCPP induced concentration-dependent ERK phosphorylation in 5-HT2B positive primary cells.

Conclusions

Activation of the 5-HT2B receptors may stimulate cell proliferation and angiogenesis and therefore alter the vascular system of the dura mater, which may result in a higher susceptibility for migraine.

No conflict of interest.

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Correspondence to M Kremser.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Kremser, M., Hunfeld, A. & Lübbert, H. EHMTI-0093. Investigation of 5-HT2B receptor pathways with relevance to a mouse migraine model. J Headache Pain 15, F13 (2014). https://doi.org/10.1186/1129-2377-15-S1-F13

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  • DOI: https://doi.org/10.1186/1129-2377-15-S1-F13

Keywords

  • Migraine
  • Dura Mater
  • Chronic Migraine
  • mCPP
  • Neurogenic Inflammation