An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system. (Department of Neurology, University of Essen, Essen, Germany) Pain. 2001;92:101-106.

Abstract

This report described a new rat model, which allowed the study of calcitonin gene related peptide (CGRP) release from the meninges into venous blood following activation of the trigeminal vascular system. The effects of classical and new antimigraine drugs as acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl] benzonitrile) were evaluated in comparison with the established model of neurogenic inflammation in the meninges. Sumatriptan and donitriptan inhibited CGRP release as well as neurogenic inflammation. ASA, however, attenuated neurogenic inflammation, but not CGRP release, confirming the concept of prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the further study of prejunctional pharmacology and mechanisms of neuropeptide release in the trigeminal vascular system, which might be crucial for the further development of potent, more effective anti-migraine drugs. Comment by Leland Lou Basic migraine headache research report with the goal of establishing trigeminal stimulation in rats as an equivalent substitute for the cat model and superior sagittal sinus stimulation is discussed. The 5-HT receptor agonists appeared to be more efficacious than inflammation suppression with NSAIDs alone. Within the 5-HT receptor agonists group, donitriptan had a statistical benefit greater than sumitriptan. In summary the rat model results are similar to the cat migraine model with an increase in calcitonin gene related peptide levels and neurogenic inflammation.