Fig. 1

The Calcitonin-gene related peptide (CGRP)-signaling in the trigeminovascular system. The CGRP released from perivascular afferents in the dura, causes dilation of arterial vessels (AV). Nitric oxide (NO) from the vascular endothelium facilitates CGRP release. The CGRP signals to trigeminal ganglion neurons (Aδ/C) CGRP-ergic receptors inducing facilitation of nociceptive transmission to second-order neurons possibly by increasing the release of the excitatory neurotransmitter glutamate (Glu) from neighboring primary afferent terminals. CGRP may also signal directly to second-order neurons (dotted arrows). Adapted with permission from [11].