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-convul...

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Published in:	Neurobiology of disease 2010-02, Vol.37 (2), p.314-323
Main Authors:	Andreou, Anna P, Shields, Kevin G, Goadsby, Peter J
Format:	Article
Language:	eng
Subjects:	Amines - pharmacology Animals Anticonvulsants - pharmacology Cerebral Arteries - innervation Cerebral Arteries - physiopathology Cyclohexanecarboxylic Acids - pharmacology Disease Models, Animal GABA GABA Agonists - pharmacology GABA Antagonists - pharmacology GABA-A Receptor Agonists GABA-A Receptor Antagonists GABA-B Receptor Agonists GABA-B Receptor Antagonists gamma-Aminobutyric Acid - pharmacology Male Migraine Migraine Disorders - drug therapy Migraine Disorders - metabolism Migraine Disorders - physiopathology Neural Inhibition - drug effects Neural Inhibition - physiology Neurology Nociceptors - drug effects Nociceptors - physiology Rats Rats, Sprague-Dawley Receptors, GABA - drug effects Receptors, GABA - physiology Receptors, GABA-A - metabolism Receptors, GABA-B - metabolism Sensory Receptor Cells - drug effects Sensory Receptor Cells - physiology Synaptic Transmission - drug effects Synaptic Transmission - physiology Thalamus Trigeminal Trigeminal Nerve - drug effects Trigeminal Nerve - physiology Valproate Valproic Acid - pharmacology Ventral Thalamic Nuclei - drug effects Ventral Thalamic Nuclei - physiology
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Summary:	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 GABAA and GABAB agonists muscimol and baclofen, respectively, and the antagonists bicuculline (GABAA ) and hydroxysaclofen (GABAB ). Results: GABA inhibited the response to SSS stimulation and l -glutamate ejection. Both the selective GABAA receptor agonist muscimol, and the GABAB 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. Interpretation: These results indicate that GABAA and GABAB 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 GABAA receptor mechanisms, whereas gabapentin does not alter trigeminovascular nociception.
ISSN:	0969-9961 1095-953X