Serotonin receptors modulate trigeminovascular responses in ventroposteromedial nucleus of thalamus: a migraine target?
Triptans, serotonin 5-HT(1B/1D), receptor agonists, which are so effective in acute migraine, are considered to act directly on the trigeminovascular system. Using an in vivo model of trigeminovascular nociception, we report a potentially novel action for the triptans within the somatosensory thalamus. Both microiontophoretically applied and intravenous naratriptans potently and reversibly modulate nociceptive neurotransmission by trigeminovascular thalamic neurons in the ventroposteromedial nucleus (VPM) driven by stimulation of the superior sagittal sinus. Naratriptan also suppresses l-glutamate activated trigeminovascular VPM neurons. Co-ejection of naratriptan with the 5-HT(1B/1D) receptor antagonist GR127935 antagonized this effect. (S)-WAY 100135 the 5-HT(1A) receptor antagonist also partially inhibited the effect of naratriptan in the VPM when co-ejected with it. Taken together, the new data suggest a potential effect of triptans in the VPM nucleus of the thalamus acting through 5-HT(1A/1B/1D) mechanisms, and offer an entirely new direction for the development of and understanding of the effects of anti-migraine medicines.
Shields
Kevin G
KG
Headache Group, Institute of Neurology, London, UK.
Goadsby
Peter J
PJ
D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002536:Cerebral Arteries / Q000294:innervation* / Q000503:physiopathology; D004347:Drug Interactions / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010880:Piperidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014363:Tryptamines / Q000494:pharmacology; D020651:Ventral Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D012701:Serotonin; D018698:Glutamic Acid; C106783:naratriptan