Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor.
BACKGROUND
Nitrovasodilators, such as glyceroltrinitrate (GTN), which produce nitric oxide (NO) in the organism, are known to cause delayed headaches in migraineurs, accompanied by increased plasma levels of calcitonin gene-related peptide (CGRP) in the cranial venous outflow. Increases in plasma CGRP and NO metabolites have also been found in spontaneous migraine attacks. In a rat model of meningeal nociception, infusion of NO donors induced activity of neurons in the spinal trigeminal nucleus.


METHODS
Isoflurane-anaesthetised rats were intravenously infused with GTN (250 µg/kg) or saline for two hours and fixed by perfusion after a further four hours. Cryosections of dissected trigeminal ganglia were immunostained for detection of CGRP and neuronal NO synthase (nNOS). The ganglion neurons showing immunofluorescence for either of these proteins were counted.


RESULTS
The proportions of CGRP- and nNOS- as well as double-immunopositive neurons were increased after GTN infusion compared to saline treatment in all parts of the trigeminal ganglion (CGRP) or restricted to the ophthalmic region (nNOS). The size of immunopositive neurons was not significantly different compared to controls.


CONCLUSIONS
High levels of NO may induce the expression or availability of CGRP and nNOS. Similar changes may be involved in nitrovasodilator-induced and spontaneous headache attacks in migraineurs.
Institute of Physiology and Pathophysiology, University of Erlangen-Nuernberg, Universitaetsstrasse 17, Erlangen, Germany.
Anne
A
Dieterle
Michael J M
MJ
Fischer
Andrea S
AS
Link
Winfried L
WL
Neuhuber
Karl
K
Messlinger
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008881:Migraine Disorders / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D015740:Calcitonin Gene-Related Peptide