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.Met...
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doaj-0fb6432605d04a7386eac994eef574da2021-03-20T04:58:28ZengElsevierNeurobiology of Disease1095-953X2010-02-01372314323GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamusAnna P. Andreou0Kevin G. Shields1Peter J. Goadsby2Headache Group - Department of Neurology, University of California, San Francisco, San Francisco, CA, USAThe National Hospital for Neurology and Neurosurgery, Queen Square, London, UKHeadache Group - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Corresponding author. Headache Group-Department of Neurology, University of California, San Francisco, 1635 Divisadero St, San Francisco CA 94115, USA.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.http://www.sciencedirect.com/science/article/pii/S0969996109002848TrigeminalThalamusGABAValproateMigraine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna P. Andreou Kevin G. Shields Peter J. Goadsby |
spellingShingle |
Anna P. Andreou Kevin G. Shields Peter J. Goadsby GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus Neurobiology of Disease Trigeminal Thalamus GABA Valproate Migraine |
author_facet |
Anna P. Andreou Kevin G. Shields Peter J. Goadsby |
author_sort |
Anna P. Andreou |
title |
GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
title_short |
GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
title_full |
GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
title_fullStr |
GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
title_full_unstemmed |
GABA and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
title_sort |
gaba and valproate modulate trigeminovascular nociceptive transmission in the thalamus |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2010-02-01 |
description |
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. |
topic |
Trigeminal Thalamus GABA Valproate Migraine |
url |
http://www.sciencedirect.com/science/article/pii/S0969996109002848 |
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