title: Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine?
abstract: 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 beta 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 beta 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 beta2 antagonist ICI 118,551 had no effect (SSS, P = 0.9; L-glutamate, P = 0.4), nor did the beta2 agonist procaterol (SSS, P = 0.6; L-glutamate, P = 0.9). SR 59230A (beta3 antagonist) also produced no significant inhibition (SSS, P = 0.7; L-glutamate, P = 0.2), indicating an inhibitory role for beta1 antagonists only. beta Blockers therefore may exert some of their therapeutic effects in migraine through beta1 adrenoceptor antagonist actions in the thalamus. Thalamic involvement in migraine is attractive given the complex and widespread nature of the sensory disturbance.
authors.affiliation: Headache Group, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Shields
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D007478:Iontophoresis / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D014276:Trigeminal Nerve / Q000187:drug effects / Q000503:physiopathology*; D020651:Ventral Thalamic Nuclei / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011412:Propanolamines; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C081293:WAY 100135; D018698:Glutamic Acid; C026777:ICI 118551; D001262:Atenolol; D011433:Propranolol; D007545:Isoproterenol; D017265:Procaterol