Role of CGRP Receptors in Cerebral Blood Flow Increase Upon Trigeminovascular Activation in Rats: An Implication of CGRP Mechanism of Migraine Attacks

摘要

To explore the role of calcitonin gene-related peptide (CGRP) receptors in acute migraine attacks, the cerebral blood flow change was investigated in rat trigemiovascular activation model utilizing CGRP receptor antagonist. In the rats, both parietal cortical blood flow (CoBF) on the right side and thalamic blood flow (ThBF) on the left side were continuously monitored with the Laser-Doppler flow meter system. CoBF and ThBF were measured before and after the electrical stimulation of nasociliary nerve (NCN) under intravenous injection of hCGRP 8-37 followed by 5-HT_(1B/1D) receptor agonist, sumatriptan. Both CoBF and ThBF were significantly increased upon electrical NCN stimulation at 30 sec from the initiation of stimulation in control state. These increase were significantly suppressed after hCGRP 8-37 administration. They were also suppressed after sumatriptan administration. This study demonstrated that CGRP receptor antagonist attenuated the blood flow increase upon trigeminal nerve stimulation as much as that by 5-HT_(1B/1D) agonists. CGRP is the most important neurotransmitter substance in the trigeminal neurogenic vasodilatation.