EFFECT OF A SEROTONIN AGONIST (SUMATRIPTAN) ON THE PEPTIDERGIC INNERVATION OF THE RAT CEREBRAL DURA-MATER AND ON THE EXPRESSION OF C-FOS INTHE CAUDAL TRIGEMINAL NUCLEUS IN AN EXPERIMENTAL MIGRAINE MODEL

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation including nociceptive axons and their termina ls, which display intense calcitonin gene-related peptide (CGRP) immun oreactivity both in the connective tissue and around blood vessels, St ereotactic electrical stimulation of the trigeminal (Gasserian) gangli on, regarded as an experimental migraine model, induces marked increas e and disintegration of club-like perivascular CGRP-immunopositive ner ve endings in the dura, Intravenous administration of sumatriptan, pri or to electrical stimulation, prevents disintegration of perivascular terminals and induces accumulation of CGRP ill terminal and pretermina l portions of peripheral sensory axons, Consequently, immunopositive t erminals and varicosities increase in size; accumulation of axoplasmic organelles results in a ''hollow'' appearance of many varicosities, S ince sumatriptan exerts its anti-migraine effect by virtue of its agon ist action on 5-HT1D receptors, we suggest that sumatriptan prevents t he release of CORP from dural perivascular terminals by an action at 5 -HT1D receptors, In the caudal trigeminal nucleus electrical stimulati on of the trigeminal ganglion induces, in interneurons, increased expr ession of the oncoprotein c-fos which is not prevented by intravenous application of sumatriptan. Disparate findings regarding this effect a re partly due to the fact that sumatriptan very poorly passes the bloo d-brain barrier and partly to different experimental paradigms used by different authors. (C) 1997 Wiley-Liss, Inc.