title: GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus.
abstract: OBJECTIVE
  To study the role of GABA receptors in thalamic relay neurons in the ventroposteromedial (VPM) nucleus of the rat activated by a trigeminovascular nociceptive stimulus in relationship to migraine, and the potential modulation of nociceptive transmission by GABA acting anti-convulsants.
  
  
  METHODS
  Trigeminovascular nociceptive afferents were identified in the VPM by electrical stimulation of the superior sagittal sinus (SSS), and cell bodies identified by activation with L-glutamate. The effect of GABA, valproate and gabapentin ejection during SSS stimulation and microiontophoresis of L-glutamate was studied. GABA responses were characterized with the selective GABA(A) and GABA(B) agonists muscimol and baclofen, respectively, and the antagonists bicuculline (GABA(A)) and hydroxysaclofen (GABA(B)).
  
  
  RESULTS
  GABA inhibited the response to SSS stimulation and L-glutamate ejection. Both the selective GABA(A) receptor agonist muscimol, and the GABA(B) agonist baclofen strongly inhibited the post-synaptic response to L-glutamate. This inhibition could be antagonised by co-ejection of the appropriate antagonist. The post-synaptic inhibitory action of GABA on the cell bodies of third order neurons could be partially antagonised by co-ejection of bicuculline but not by hydroxysaclofen. Valproate inhibited the responses to SSS stimulation and L-glutamate ejection. Bicuculline, but not hydroxysaclofen, was able to antagonise the effect of valproate on both responses to L-glutamate and SSS stimulation. Gabapentin did not alter the responses to L-glutamate and SSS stimulation.
  
  
  CONCLUSIONS
  These results indicate that GABA(A) and GABA(B) receptors on thalamic neurons can modulate trigeminovascular nociceptive transmission in the VPM nucleus. Sodium valproate can inhibit trigeminovascular nociception at the level of VPM through GABA(A) receptor mechanisms, whereas gabapentin does not alter trigeminovascular nociception.
authors.affiliation: Headache Group - Department of Neurology, University of California, San Francisco, San Francisco, CA 94115, USA.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Andreou
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Shields
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002536:Cerebral Arteries / Q000294:innervation / Q000503:physiopathology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D000077206:Gabapentin; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*; D014635:Valproic Acid / Q000494:pharmacology; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin