Effects of eletriptan on the peptidergic innervation of the cerebral dura mater and trigeminal ganglion, and on the expression of c-fos and c-jun in the trigeminal complex of the rat in an experimental migraine model.
Nociceptive axons and terminals in the supratentorial cerebral dura mater display an intense calcitonin gene-related peptide (CGRP) immunoreactivity. In an experimental migraine model, it has been shown that electrical stimulation of the rat trigeminal ganglion induced an increase in the lengths of CGRP-immunoreactive axons, increased size and number of pleomorphic axonal varicosities in the dura mater, and an increased number of c-jun and c-fos protein-expressing nerve cells in the trigeminal complex. We demonstrate the effect of the highly specific and moderately lipophilic serotonin agonist eletriptan (Pfizer) which prevents the effects of electrical stimulation in the dura mater. Eletriptan also affected the caudal trigeminal complex; it markedly reduced the numbers of the oncoprotein-expressing cells, mainly after stimulation and to some extent also in nonstimulated animals. Eletriptan also affected expression of CGRP in perikarya of trigeminal ganglion cells, insofar as the number of small nerve cells exhibiting a compact CGRP immunoreaction was decreased to one quarter of the original value. In all these respects, eletriptan acted in a similar way to sumatriptan, with the notable exception that eletriptan also blocked the stimulation-induced effects in the nucleus caudalis trigemini and the upper cervical spinal cord (trigeminal complex), whereas sumatriptan did not. It is concluded that eletriptan, acting on perikarya and both the peripheral and the central axon terminals of primary sensory neurons, exerts its antimigraine effect by an agonist action on 5-HT1B/1D receptors throughout the entire trigeminal system, probably by passing the blood-brain-barrier because of its lipophilic character.
Knyihár-Csillik
E
E
Department of Clinical Neurology, Szeged University, Semmelweis utca 6, H-6701 Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu
Tajti
J
J
Csillik
A E
AE
Chadaide
Z
Z
Mihály
A
A
Vécsei
L
L
D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000502:physiology; D004195:Disease Models, Animal; D004388:Dura Mater / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D018170:Sumatriptan / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology*; D014363:Tryptamines
D007211:Indoles; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011759:Pyrrolidines; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C115647:eletriptan; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide