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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3621957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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