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Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats
BACKGROUND: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. ME...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Pain Society
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322658/ https://www.ncbi.nlm.nih.gov/pubmed/37394274 http://dx.doi.org/10.3344/kjp.23039 |
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author | Zhai, QingLing Wang, KaiXin Zhang, Defu Chen, Jinbo Dong, XiaoMeng Pan, Yonghui |
author_facet | Zhai, QingLing Wang, KaiXin Zhang, Defu Chen, Jinbo Dong, XiaoMeng Pan, Yonghui |
author_sort | Zhai, QingLing |
collection | PubMed |
description | BACKGROUND: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. METHODS: Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 μg/kg and 100 μg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis. RESULTS: Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In in vitro studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway. CONCLUSIONS: This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway. |
format | Online Article Text |
id | pubmed-10322658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Korean Pain Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-103226582023-07-07 Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats Zhai, QingLing Wang, KaiXin Zhang, Defu Chen, Jinbo Dong, XiaoMeng Pan, Yonghui Korean J Pain Experimental Research Articles BACKGROUND: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. METHODS: Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 μg/kg and 100 μg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis. RESULTS: Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In in vitro studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway. CONCLUSIONS: This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway. The Korean Pain Society 2023-07-01 2023-07-01 /pmc/articles/PMC10322658/ /pubmed/37394274 http://dx.doi.org/10.3344/kjp.23039 Text en © The Korean Pain Society, 2023 https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Experimental Research Articles Zhai, QingLing Wang, KaiXin Zhang, Defu Chen, Jinbo Dong, XiaoMeng Pan, Yonghui Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title | Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title_full | Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title_fullStr | Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title_full_unstemmed | Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title_short | Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats |
title_sort | perampanel ameliorates nitroglycerin-induced migraine through inhibition of the camp/pka/creb signaling pathway in the trigeminal ganglion in rats |
topic | Experimental Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322658/ https://www.ncbi.nlm.nih.gov/pubmed/37394274 http://dx.doi.org/10.3344/kjp.23039 |
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