Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig.

Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca(2+) removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.

Pain pharmacology in migraine: focus on CGRP and CGRP receptors.

Over the last 100 years, the discovery of new analgesics has been a complex and difficult task. However, remarkable progress in the identification of novel molecular targets relevant for pain medicines has been reported. Here we will focus on the neuropeptide calcitonin generelated peptide (CGRP) and its receptors (CGRP-R) because of their role in migraine mechanism and migraine therapy. Recent preclinical and clinical data on the localisation, regulation and plasma levels of CGRP and on the function of CGRP-R will be summarised. The reviewed findings highlight the major function of CGRP in migraine and the use of CGRP-R antagonists as a novel approach for the treatment of migraine attack and, perhaps, as migraine prophylactic medicines.