Suppression by eletriptan of the activation of trigeminovascular sensory neurons by glyceryl trinitrate.
The effect of intracarotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate vascular headache, on the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Cats were anaesthetised with alpha-chloralose, immobilised and artificially ventilated. The superior sagittal sinus (SSS) was isolated and stimulated electrically. Facial receptive fields (RF) were also stimulated. Single neurons were recorded from the trigeminal nucleus caudalis with a metal microelectrode equipped with six glass barrels for microiontophoresis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (mean rate 19+/-7, range 5-100 microg kg(-1) min(-1), in a volume of 2 ml min(-1)) increased the spontaneous discharge rate of second-order neurons which received dural and facial sensory input to 429+/-80% of control. Iontophoretic application of the 5-HT(1B/1D) receptor agonist eletriptan (50 nA) at the peak of the response decreased the discharge rate of neurons towards pre-GTN control levels. In the presence of continuous iontophoretic application of the 5-HT(1B/1D) receptor antagonist GR127935, the decrease in discharge rate caused by eletriptan was antagonised. We conclude (1) that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN and (2) that the antimigraine agent eletriptan is able to selectively suppress noxious sensory information from the dura, induced by GTN, via an action at 5-HT(1B/1D) receptors.
Lambert
G A
GA
Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, University of New South Wales, Australia. g.lambert@unsw.edu.au
Boers
P M
PM
Hoskin
K L
KL
Donaldson
C
C
Zagami
A S
AS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004347:Drug Interactions; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D009475:Neurons, Afferent / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects*; D014363:Tryptamines; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D007211:Indoles; D011759:Pyrrolidines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014665:Vasodilator Agents; C115647:eletriptan; D005996:Nitroglycerin