GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus

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 postsynaptic 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 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. (c) 2009 Elsevier Inc. All rights reserved.