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Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury

Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aim...

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Autores principales: Zhao, Liang, Li, Dan, Liu, Nan, Liu, Lu, Zhang, Zhuo, Gao, Chao, Kawano, Hitoshi, Zhou, Fang-Yuan, Li, Hong-Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113736/
https://www.ncbi.nlm.nih.gov/pubmed/30152258
http://dx.doi.org/10.1177/1744806918796057
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author Zhao, Liang
Li, Dan
Liu, Nan
Liu, Lu
Zhang, Zhuo
Gao, Chao
Kawano, Hitoshi
Zhou, Fang-Yuan
Li, Hong-Peng
author_facet Zhao, Liang
Li, Dan
Liu, Nan
Liu, Lu
Zhang, Zhuo
Gao, Chao
Kawano, Hitoshi
Zhou, Fang-Yuan
Li, Hong-Peng
author_sort Zhao, Liang
collection PubMed
description Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aimed to assess whether the inhibition of aquaporin 4 had an analgesic effect on neuropathic pain and whether the inhibition of astrocytic activation and ERK pathway was involved in the analgesic effect of TGN-020. We thus found that TGN-020 upregulated the threshold of thermal and mechanical allodynia, downregulated the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α, attenuated the astrocytic activation and suppressed the activation of mitogen-activated protein kinase pathways in the spinal dorsal horn and dorsal root ganglion. Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury–induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.
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spelling pubmed-61137362018-09-04 Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury Zhao, Liang Li, Dan Liu, Nan Liu, Lu Zhang, Zhuo Gao, Chao Kawano, Hitoshi Zhou, Fang-Yuan Li, Hong-Peng Mol Pain Research Article Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aimed to assess whether the inhibition of aquaporin 4 had an analgesic effect on neuropathic pain and whether the inhibition of astrocytic activation and ERK pathway was involved in the analgesic effect of TGN-020. We thus found that TGN-020 upregulated the threshold of thermal and mechanical allodynia, downregulated the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α, attenuated the astrocytic activation and suppressed the activation of mitogen-activated protein kinase pathways in the spinal dorsal horn and dorsal root ganglion. Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury–induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion. SAGE Publications 2018-08-28 /pmc/articles/PMC6113736/ /pubmed/30152258 http://dx.doi.org/10.1177/1744806918796057 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Zhao, Liang
Li, Dan
Liu, Nan
Liu, Lu
Zhang, Zhuo
Gao, Chao
Kawano, Hitoshi
Zhou, Fang-Yuan
Li, Hong-Peng
Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title_full Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title_fullStr Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title_full_unstemmed Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title_short Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury
title_sort correlation of tgn-020 with the analgesic effects via erk pathway activation after chronic constriction injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113736/
https://www.ncbi.nlm.nih.gov/pubmed/30152258
http://dx.doi.org/10.1177/1744806918796057
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