Brain, Vol 120, Issue 12 2171-2177, Copyright © 1997 by Oxford University Press
RJ Storer and PJ Goadsby
Migraine is a common and debilitating condition. Its treatment has received
considerable attention in recent times with the introduction into clinical
use of the 5HT1B/1D agonist sumatriptan. It is known from human studies
that the intracranial blood vessels and dura mater are important
pain-producing structures since mechanical or electrical stimulation of
these vessels, such as the superior sagittal sinus, causes pain. We have
developed a model of craniovascular pain by stimulating the superior
sagittal sinus and monitoring trigeminal neuronal activity using
electrophysiological techniques. Cats were anaesthetized with
alpha-chloralose (60 mg/kg, intraperitoneally), paralysed (gallamine 6
mg/kg, intravenously) and ventilated. The superior sagittal sinus was
accessed and isolated for electrical stimulation by a mid-line circular
craniotomy. The region of the dorsal surface of C2 spinal cord was exposed
by a laminectomy and an electrode placed for recording evoked activity from
sinus stimulation and spontaneous activity of the same cells. The electrode
was a custom-made seven barrel glass microelectrode with the central barrel
containing a tungsten recording wire. Signals were amplified and monitored
on-line using a custom-written sampling program. Cells were recorded that
were activated by electrical stimulation of the sinus and were also
spontaneously activated. Cells fired with latencies consistent with A delta
and C fibres, generally firing three or four times per stimulus (0.3 Hz,
250 microseconds duration, 100 V) delivered to the sinus. Both evoked and
spontaneous firing could be inhibited by iontophoresis of ergometrine (9/10
cells), sumatriptan (2/3 cells) and zolmitriptan (9/15 cells) but not by
saline (3/10 cells). These data are the first demonstration of inhibition
of second order trigeminal neurons by direct local application of 5HT1B/1D
agonists. Although intravenous administration of these compounds has
demonstrated inhibition of sinus evoked firing in previous studies, it is
not possible using the intravenous route to be clear at which anatomical
site inhibition is taking place, whereas microiontophoresis offers a clear
locus of action. These data demonstrate that the second order trigeminal
nucleus synapse in the brainstem and upper cervical cord is the most likely
site of action for brain penetrant anti-migraine drugs of the 5HT1B/1D
class.
ARTICLES
Microiontophoretic application of serotonin (5HT)1B/1D agonists inhibits trigeminal cell firing in the cat
Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
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