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Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-ev...

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Autores principales: Ji, Xi-Tuan, Qian, Nian-Song, Zhang, Tao, Li, Jin-Mao, Li, Xin-Kui, Wang, Peng, Zhao, Dong-Sheng, Huang, Gang, Zhang, Lei, Fei, Zhou, Jia, Dong, Niu, Le
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621957/
https://www.ncbi.nlm.nih.gov/pubmed/23585846
http://dx.doi.org/10.1371/journal.pone.0060733
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author Ji, Xi-Tuan
Qian, Nian-Song
Zhang, Tao
Li, Jin-Mao
Li, Xin-Kui
Wang, Peng
Zhao, Dong-Sheng
Huang, Gang
Zhang, Lei
Fei, Zhou
Jia, Dong
Niu, Le
author_facet Ji, Xi-Tuan
Qian, Nian-Song
Zhang, Tao
Li, Jin-Mao
Li, Xin-Kui
Wang, Peng
Zhao, Dong-Sheng
Huang, Gang
Zhang, Lei
Fei, Zhou
Jia, Dong
Niu, Le
author_sort Ji, Xi-Tuan
collection PubMed
description Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and “Astrocyte-Cytokine-NMDAR-neuron” pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.
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spelling pubmed-36219572013-04-12 Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model Ji, Xi-Tuan Qian, Nian-Song Zhang, Tao Li, Jin-Mao Li, Xin-Kui Wang, Peng Zhao, Dong-Sheng Huang, Gang Zhang, Lei Fei, Zhou Jia, Dong Niu, Le PLoS One Research Article Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and “Astrocyte-Cytokine-NMDAR-neuron” pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP. Public Library of Science 2013-04-09 /pmc/articles/PMC3621957/ /pubmed/23585846 http://dx.doi.org/10.1371/journal.pone.0060733 Text en © 2013 Ji et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ji, Xi-Tuan
Qian, Nian-Song
Zhang, Tao
Li, Jin-Mao
Li, Xin-Kui
Wang, Peng
Zhao, Dong-Sheng
Huang, Gang
Zhang, Lei
Fei, Zhou
Jia, Dong
Niu, Le
Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title_full Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title_fullStr Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title_full_unstemmed Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title_short Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
title_sort spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621957/
https://www.ncbi.nlm.nih.gov/pubmed/23585846
http://dx.doi.org/10.1371/journal.pone.0060733
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