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The Journal of Headache and Pain

, 16:57

First Online: 24 June 2015Received: 27 March 2015Accepted: 05 June 2015

Abstract

BackgroundThe capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two in vivo models of migraine.

MethodsMale Sprague–Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene c-fos was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.

ResultsInflammatory up-regulation of c-fos in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.

ConclusionOur results describe two TRPV1 antagonists that are effective in two in vivo models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.

KeywordsTransient receptor potential vanilloid 1 Capsaicin Calcitonin gene-related peptide Inflammatory soup c-fos Trigeminal activation Jannis E Meents and Jan Hoffmann contributed equally to this work.

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Autor: Jannis E Meents - Jan Hoffmann - Sandra R Chaplan - Lars Neeb - Sigrid Schuh-Hofer - Alan Wickenden - Uwe Reuter

Fuente: https://link.springer.com/



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