Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist
Version of Record online: 29 JAN 2009
1999 Nature Publishing Group
British Journal of Pharmacology
Volume 126, Issue 6, pages 1478–1486, March 1999
How to Cite
Cumberbatch, M. J., Williamson, D. J., Mason, G. S., Hill, R. G. and Hargreaves, R. J. (1999), Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist. British Journal of Pharmacology, 126: 1478–1486. doi: 10.1038/sj.bjp.0702444
- Issue online: 29 JAN 2009
- Version of Record online: 29 JAN 2009
- (Received August 28, 1998, Revised December 10, 1998, Accepted December 24, 1998)
- 5HT1B/1D receptors;
- trigeminal nucleus caudalis;
- dura mater;
- central sensitization;
Migraine headache pain is thought to result from an abnormal distention of intracranial, extracerebral blood vessels and the consequent activation of the trigeminal nervous system. Migraine is also often accompanied by extracranial sensory disturbances from facial tissues. These experiments investigate whether meningeal dilation produces central sensitization of neurones that receive convergent input from the face.
Single unit extracellular activity was recorded from the trigeminal nucleus caudalis of anaesthetized rats in response to either noxious stimulation of the dura mater, innocuous stimulation of the vibrissae or to a transient dilation of the meningeal vascular bed.
Rat α-CGRP (calcitonin gene-related peptide; 1 μg kg−1, i.v.) caused a dilation of the middle meningeal artery and facilitated vibrissal responses by 36±7%.
The 5-HT1B/1D agonist, L-741,604 (3 mg kg−1, i.v.), inhibited responses to noxious stimulation of the dura mater (16±7% of control) and, in a separate group of animals, blocked the CGRP-evoked facilitation of vibrissal responses.
L-741,604 (3 mg kg−1, i.v.) also inhibited responses to innocuous stimulation of the vibrissa (14±10% of control) with neurones that received convergent input from the face and from the dura mater, but not with cells that received input only from the face (70±12% of control).
These data show that dilation of meningeal blood vessels causes a sensitization of central trigeminal neurones and a facilitation of facial sensory processing which was blocked by activation of pre-synaptic 5-HT1B/1D receptors.
Sustained dural blood vessel dilation during migraine may cause a sensitization of trigeminal neurones. This may underlie some of the symptoms of migraine, such as the headache pain and the extracranial allodynia. Inhibition of this central sensitization may therefore offer a novel strategy for the development of acute and/or prophylactic anti-migraine therapies.
British Journal of Pharmacology (1999) 126, 1478–1486; doi:10.1038/sj.bjp.0702444