Abstract :
[en] Infusion of nitric oxide (NO) donors is known to induce delayed attacks of
migraine and cluster headache or aggravate tension-type headaches in patients
suffering from these primary headaches. Previously we have reported that
infusion of NO donors in the rat causes delayed neuronal activity in the spinal
trigeminal nucleus, which parallels the above clinical observations. Suggesting
that endogenous NO production is involved in the generation of primary
headaches, we used this animal model of meningeal nociception to determine
whether a prolonged increase in NO levels causes an increase in neuronal
activity. In anaesthetized rats spinal trigeminal neurons with afferent input
from the exposed dura were recorded. Continuous intravenous infusion of the
NO donors sodium nitroprusside (25 mg/kg/h) or glycerol trinitrate (250 mg/
kg/h) for 2 h induced a persisting increase in neuronal activity but
no change in systemic blood pressure. In this activated trigeminal system the
calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS (900 mg/
kg) was infused. Spinal trigeminal activity was significantly reduced within
minutes and to a similar extent as previously reported in animals not treated
with NO. Slow continuous NO infusion may be a model of the active headache
phase, and inhibition of CGRP receptors can reverse the induced neuronal
activity.
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