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Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model

Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. S...

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Autores principales: Zhang, Enji, Yi, Min-Hee, Shin, Nara, Baek, Hyunjung, Kim, Sena, Kim, Eunjee, Kwon, Kisang, Lee, Sunyeul, Kim, Hyun-Woo, Chul Bae, Yong, Kim, Yonghyun, Kwon, O.-Yu, Lee, Won Hyung, Kim, Dong Woon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479804/
https://www.ncbi.nlm.nih.gov/pubmed/26109318
http://dx.doi.org/10.1038/srep11555
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author Zhang, Enji
Yi, Min-Hee
Shin, Nara
Baek, Hyunjung
Kim, Sena
Kim, Eunjee
Kwon, Kisang
Lee, Sunyeul
Kim, Hyun-Woo
Chul Bae, Yong
Kim, Yonghyun
Kwon, O.-Yu
Lee, Won Hyung
Kim, Dong Woon
author_facet Zhang, Enji
Yi, Min-Hee
Shin, Nara
Baek, Hyunjung
Kim, Sena
Kim, Eunjee
Kwon, Kisang
Lee, Sunyeul
Kim, Hyun-Woo
Chul Bae, Yong
Kim, Yonghyun
Kwon, O.-Yu
Lee, Won Hyung
Kim, Dong Woon
author_sort Zhang, Enji
collection PubMed
description Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.
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spelling pubmed-44798042015-06-29 Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model Zhang, Enji Yi, Min-Hee Shin, Nara Baek, Hyunjung Kim, Sena Kim, Eunjee Kwon, Kisang Lee, Sunyeul Kim, Hyun-Woo Chul Bae, Yong Kim, Yonghyun Kwon, O.-Yu Lee, Won Hyung Kim, Dong Woon Sci Rep Article Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli. Nature Publishing Group 2015-06-25 /pmc/articles/PMC4479804/ /pubmed/26109318 http://dx.doi.org/10.1038/srep11555 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Enji
Yi, Min-Hee
Shin, Nara
Baek, Hyunjung
Kim, Sena
Kim, Eunjee
Kwon, Kisang
Lee, Sunyeul
Kim, Hyun-Woo
Chul Bae, Yong
Kim, Yonghyun
Kwon, O.-Yu
Lee, Won Hyung
Kim, Dong Woon
Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title_full Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title_fullStr Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title_full_unstemmed Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title_short Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
title_sort endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479804/
https://www.ncbi.nlm.nih.gov/pubmed/26109318
http://dx.doi.org/10.1038/srep11555
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