Fig. 1

Scheme of sources and sinks for CGRP (curved arrows) in the trigeminovascular system, ameninges, b trigeminal ganglion and spinal trigeminal nucleus. CGRP released from trigeminal afferent fibers innervating dural arteries (DA) is most likely taken up from capillaries, venous vessels (DV) and possibly the superior sagittal sinus (SSS), and is transported with the blood stream into the internal jugular vein. The same may occur in the trigeminal ganglion, which is located outside the blood-brain barrier (BBB). However, a BBB is functional in pial arteries (PA) and veins (PV). Thus, CGRP released from perivascular afferent fibres cannot enter the vessels but diffuses into the surrounding cerebrospinal rooms, the subarachnoidal space or the cerebello-medullary cisterna (cisterna magna), respectively, where it can be found in the cerebrospinal fluid (CSF). Probably part of it is secreted through the arachnoid granulations (AG) into the SSS and appears secondarily also in the jugular blood. CGRP released from the central terminals of trigeminal afferents within the spinal trigeminal may move out of the medulla into the cisterna magna. Innervated cortical arterioles (CA) arising from penetrating pial arteries may also be innervated by trigeminal afferents. Here, CGRP may be released into the perivascular space between the vessel wall and the surrounding astroglial end-feet. Then it may be transported with the glymphatic flow through the brain tissue and collected in the venous perivascular spaces. CGRP may move together with the extracellular fluid within these spaces along the venous vessels through the subarachnoidal space to the dura mater, where it may be finally collected in lymphatic vessels (LV) accompanying the SSS