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The Journal of Headache and Pain

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Open Access 01-12-2016 | Research article

Endovanilloids are potential activators of the trigeminovascular nocisensor complex

Authors: Mária Dux, Éva Deák, Noémi Tassi, Péter Sántha, Gábor Jancsó

Published in: The Journal of Headache and Pain | Issue 1/2015

Abstract

Background

In the dura mater encephali a significant population of trigeminal afferents coexpress the nociceptive ion channel transient receptor potential vanilloid type 1 (TRPV1) receptor and calcitonin gene-related peptide (CGRP). Release of CGRP serves the central transmission of sensory information, initiates local tissue reactions and may also sensitize the nociceptive pathway. To reveal the possible activation of meningeal TRPV1 receptors by endogenously synthetized agonists, the effects of arachidonylethanolamide (anandamide) and N-arachidonoyl-dopamine (NADA) were studied on dural vascular reactions and meningeal CGRP release.

Methods

Changes in meningeal blood flow were measured with laser Doppler flowmetry in a rat open cranial window preparation following local dural applications of anandamide and NADA. The release of CGRP evoked by endovanilloids was measured with ELISA in an in vitro dura mater preparation.

Results

Topical application of NADA induced a significant dose-dependent increase in meningeal blood flow that was markedly inhibited by pretreatments with the TRPV1 antagonist capsazepine, the CGRP antagonist CGRP_8–37, or by prior systemic capsaicin desensitization. Administration of anandamide resulted in minor increases in meningeal blood flow that was turned into vasoconstriction at the higher concentration. In the in vitro dura mater preparation NADA evoked a significant increase in CGRP release. Cannabinoid CB1 receptors of CGRP releasing nerve fibers seem to counteract the TRPV1 agonistic effect of anandamide in a dose-dependent fashion, a result which is confirmed by the facilitating effect of CB1 receptor inhibition on CGRP release and its reversing effect on the blood flow.

Conclusions

The present findings demonstrate that endovanilloids are potential activators of meningeal TRPV1 receptors and, consequently the trigeminovascular nocisensor complex that may play a significant role in the pathophysiology of headaches. The results also suggest that prejunctional CB1 receptors may modulate meningeal vascular responses.

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Title: Endovanilloids are potential activators of the trigeminovascular nocisensor complex
Authors: Mária Dux
Éva Deák
Noémi Tassi
Péter Sántha
Gábor Jancsó
Publication date: 01-12-2016
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2015
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-016-0644-7

At a glance: The STEP trials

Springer Medicine

Endovanilloids are potential activators of the trigeminovascular nocisensor complex

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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Reviewer Acknowledgment 2015