P 1.8. Ethanol causes neurogenic inflammation and vasodilalation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig

• Published in: Neuropeptides (Edinburgh) Vol. 42; no. 4; p. 475
• Main Authors: De Siena, G, Nicoletti, P, Trevisani, M, Manconi, M, Zagli, G, Benemei, S, Capone, JA, Pini, LA, Geppetti, P
• Format: Journal Article
• Language: English
• Published: 01.08.2008
• ISSN: 0143-4179

Background and aims. Ethanol (EtOH) has been recently found to stimulate primary sensory neurons by activation of the transient receptor potential vanilloid 1 (TRPV1) channel. By this mechanism EtOH releases sensory neuropeptides, thereby inducing neurogenic inflammatory responses, including calcitonin generelated peptide (CGRP)-mediated dilatation of cardiac or gastric arterial vessels. Drinking alcoholic beverages is a common trigger of migraine attacks and activation of trigeminal neurons and CGRP release are considered to play a role in migraine mechanism. Thus, we have investigated in guinea pigs whether EtOH causes neurogenic inflammatory responses in the trigeminovascular system by TRPV1 stimulation and sensory neuropeptide release. Methods and results. EtOH (3%) induced a concentration-related release of substance P (SP) and CGRP from slices of trigeminal ganglia or transverse and sagittal sinuses with attached dura mater. This response was abolished in a Ca super(2+)-free medium, by capsaicin pretreatment and by the TRPV1 antagonist, capsazepine. Administration of EtOH (intraperitoneal or intragastric) increased the Evans blue dye extravasation in transverse and sagittal sinuses with attached dura mater. This effect of EtOH was abolished by capsazepine and by the NK1 receptor antagonist, SR140333. Finally, the vasodilatatory response induced by intragastric administration of EtOH in meningeal arterial vessels was selectively abolished by capsazepine and by the CGRP receptor antagonist, BIBN4096BS. Conclusions. We conclude that EtOH administration, via TRPV1 activation and SP/CGRP release, causes neurogenic inflammatory responses, including vasodilatation of meningeal vessels, a phenomenon, that may be relevant for the mechanism by which alcohol ingestion triggers migraine attacks.