An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system

Calcitonin gene related peptide (CGRP) released from the C-fibers projectin g from the trigeminal ganglion to the meninges has been suggested to play a crucial role in the pathophysiology of headache, particularly migraine. In humans it has been shown that CGRP is released during migraine-attacks, an d this is attenuated by the administration of typical anti-migraine drugs s uch as dihydroergotamine or sumatriptan. We describe a new rat model which allows the study of CGRP release from the meninges into venous blood follow ing activation of the trigeminal vascular system. The effects of classical and new anti-migraine drugs such as acetylsalicylic acid (ASA). sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoe thyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) were evaluate d in comparison with the established model of neurogenic inflammation in th e meninges. Sumatriptan and donitriptan inhibited CGRP release as well as n eurogenic inflammation. ASA, however, attenuated neurogenic inflammation, b ut not CGRP release, confirming the concept of prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the further stud y of prejunctional pharmacology and mechanisms of neuropeptide release in t he trigeminal vascular system, which might be crucial for the further devel opment of potent. more effective anti-migraine drugs. (C) 2001 Internationa l Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.