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Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist.
Br J Pharmacol. 1999 Mar; 126(6):1478-86.BJ

Abstract

1. 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. 2. 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. 3. Rat alpha-CGRP (calcitonin gene-related peptide; 1 microg kg(-1), i.v.) caused a dilation of the middle meningeal artery and facilitated vibrissal responses by 36+/-7%. 4. 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. 5. 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). 6. 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. 7. 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.

Authors+Show Affiliations

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Center, Harlow, Essex, England.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10217543

Citation

Cumberbatch, M J., et al. "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, vol. 126, no. 6, 1999, pp. 1478-86.
Cumberbatch MJ, Williamson DJ, Mason GS, et al. Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist. Br J Pharmacol. 1999;126(6):1478-86.
Cumberbatch, M. J., Williamson, D. J., Mason, G. S., Hill, R. G., & 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(6), 1478-86.
Cumberbatch MJ, et al. Dural Vasodilation Causes a Sensitization of Rat Caudal Trigeminal Neurones in Vivo That Is Blocked By a 5-HT1B/1D Agonist. Br J Pharmacol. 1999;126(6):1478-86. PubMed PMID: 10217543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist. AU - Cumberbatch,M J, AU - Williamson,D J, AU - Mason,G S, AU - Hill,R G, AU - Hargreaves,R J, PY - 1999/4/27/pubmed PY - 1999/4/27/medline PY - 1999/4/27/entrez SP - 1478 EP - 86 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 126 IS - 6 N2 - 1. 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. 2. 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. 3. Rat alpha-CGRP (calcitonin gene-related peptide; 1 microg kg(-1), i.v.) caused a dilation of the middle meningeal artery and facilitated vibrissal responses by 36+/-7%. 4. 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. 5. 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). 6. 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. 7. 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/10217543/Dural_vasodilation_causes_a_sensitization_of_rat_caudal_trigeminal_neurones_in_vivo_that_is_blocked_by_a_5_HT1B/1D_agonist_ L2 - https://doi.org/10.1038/sj.bjp.0702444 DB - PRIME DP - Unbound Medicine ER -