Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the rat cerebral dura mater and on the expression of c-fos in the caudal trigeminal nucleus in an experimental migraine model

Abstract

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation including nociceptive axons and their terminals, which display intense calcitonin gene-related peptide (CGRP) immunoreactivity both in the connective tissue and around blood vessels. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, induces marked increase and disintegration of club-like perivascular CGRP-immunopositive nerve endings in the dura. Intravenous administration of sumatriptan, prior to electrical stimulation, prevents disintegration of perivascular terminals and induces accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increase in size; accumulation of axoplasmic organelles results in a "hollow" appearance of many varicosities. Since sumatriptan exerts its anti-migraine effect by virtue of its agonist action on 5-HT1D receptors, we suggest that sumatriptan prevents the release of CGRP from dural perivascular terminals by an action at 5-HT1D receptors. In the caudal trigeminal nucleus electrical stimulation of the trigeminal ganglion induces, in interneurons, increased expression of the oncoprotein c-fos which is not prevented by intravenous application of sumatriptan. Disparate findings regarding this effect are partly due to the fact that sumatriptan very poorly passes the blood-brain barrier and partly to different experimental paradigms used by different authors.