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Brain Advance Access originally published online on December 1, 2004
Brain 2005 128(1):86-97; doi:10.1093/brain/awh298
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Brain Vol. 128 No. 1 © Guarantors of Brain 2004; all rights reserved

Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine?

Kevin G. Shields and Peter J. Goadsby

Headache Group, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK

Correspondence to: Professor P. J. Goadsby, Institute of Neurology, Queen Square, London WC1N 3BG, UK E-mail: peterg{at}ion.ucl.ac.uk

Migraine is a common, debilitating condition affecting up to 15% of the population. The ventroposteromedial nucleus of the thalamus relays trigeminal sensory input to the primary somatosensory cortex. In vivo electrophysiological recordings were made from the cell bodies of thalamocortical relay neurons in rats. We investigated whether microiontophoretic ejection of ß antagonists could inhibit thalamocortical activity in response to superior sagittal sinus (SSS) stimulation. We also studied ‘postsynaptic’ actions of these drugs through their modulatory actions on L-glutamate-evoked third order neuronal firing. Propranolol inhibited responses to SSS stimulation (P < 0.001) and L-glutamate ejection (P < 0.001). This was due to an action on ß receptors as it could be partially reversed by co-ejection of isoproterenol (SSS, P = 0.02; L-glutamate, P = 0.006). Serotonin (5-HT) receptor antagonism did not contribute to propranolol's action since the 5-HT1A receptor antagonist, (S)-WAY 100135 (P = 0.2), and the 5-HT1B/1D receptor antagonist, GR127935 (P = 0.6), did not affect L-glutamate-evoked neuronal firing. Atenolol inhibited both responses (SSS, P = 0.003; L-glutamate, P < 0.001). The ß2 antagonist ICI 118,551 had no effect (SSS, P = 0.9; L-glutamate, P = 0.4), nor did the ß2 agonist procaterol (SSS, P = 0.6; L-glutamate, P = 0.9). SR 59230A (ß3 antagonist) also produced no significant inhibition (SSS, P = 0.7; L-glutamate, P = 0.2), indicating an inhibitory role for ß1 antagonists only. ß Blockers therefore may exert some of their therapeutic effects in migraine through ß1 adrenoceptor antagonist actions in the thalamus. Thalamic involvement in migraine is attractive given the complex and widespread nature of the sensory disturbance.


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J. Pharmacol. Exp. Ther.Home page
S. Akerman, P. R. Holland, and P. J. Goadsby
Cannabinoid (CB1) Receptor Activation Inhibits Trigeminovascular Neurons
J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 64 - 71.
[Abstract] [Full Text] [PDF]



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