Role Of Cgrp In Sensitization Of Dura Mater

The mammalian dura mater encephali is richly supplied by trigeminal nerve fibers, a considerable proportion of which contains calcitonin gene-related peptide (CGRP). As plasma levels of CGRP are increased in some forms of headaches, the question is in which way CGRP is involved in nociceptive mechanisms within the peripheral and the central trigeminovascular system.

Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat

The parietal dura mater encephali of the rat was shown by immunohistochemistry to be densely innervated by calcitonin gene related peptide (CGRP) immunoreactive nerve fibers spreading around the medial meningeal artery and its branches. Electrical stimulation of the dural surface (10–20 V, 5–10 Hz, 10–30 min) caused a depletion of CGRP-immunopositive fibers, suggesting a release of CGRP. The dural blood flow around branches of the medial meningeal artery was also monitored with a laser Doppler flowmeter. Short periods (30 s) of electrical stimulation with parameters that presumably released CGRP from nerve fibers caused a repeatable and constant increase of the blood flow for 1–2 min. This evoked increase could dose dependently be inhibited by topical application of the CGRP antagonist hCGRP8–37. Accordingly, administration of hCGRP increased the basal blood flow. We conclude that stimulation of trigeminal afferents innervating the dura mater releases CGRP from peptidergic afferent terminals, thereby causing vasodilatation and increasing the meningeal blood flow, an important element of neurogenic inflammation.Key words: dura mater encephali, afferent nerve fibers, calcitonin gene related peptide, immunohistochemistry, laser Doppler flowmetry.