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.

Infraterminal spreading and extrajunctional expression of nicotinic acetylcholine receptors in denervated rat skeletal muscle.

Through the use of biotinylated-bungarotoxin and monoclonal antibodies, the nicotinic acetylcholine receptor (nAChR) was localized in the subneural apparatus of mammalian motor end plates of the flexor digitorum brevis muscle of the adult rat at the light and electron microscopic levels. Under normal conditions, nAChR was located in the primary post-synaptic membrane of the neuromuscular junction, and the depths of the junctional folds constituting the secondary post-synaptic membrane did not contain any nAChR. Up to 75 days after repeated transection of the related motor nerve (sciatic), there was no major alteration in the light-microscopic localization of junctional nAChR in the subneural apparatus, except for a moderate shrinkage and increased immunocytochemical reactivity of the subneural apparatus. At the electron microscopic level, however, immunocytochemical reactivity gradually occupied the entire extent of the secondary post-synaptic membrane, including the depths of the junctional folds, which exhibited extensive branching. In non-innervated portions of the muscle fibers, nAChR receptor appeared in a linear localization on the surfaces of denervated muscle fibers. This linear reaction was not continuous with the nAChR reaction of the motor end plates. It is concluded that denervation supersensitivity might not be due to spreading of junctional nAChR from the end-plate area, but rather to expression of nAChR in non-innervated portions of the muscle fiber and to the infraterminal (subsynaptic) spreading of nAChR into the depths of junctional folds.