Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain

Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain

Abstract We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation...

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Autores principales: Xue-Ming Hu, Hui Zhang, Heng Xu, Hai-Long Zhang, Li-Ping Chen, Wen-Qiang Cui, Wei Yang, Wen Shen
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/96230f4ef1f241758be20b03e70e1f37
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spelling oai:doaj.org-article:96230f4ef1f241758be20b03e70e1f372021-12-02T15:06:24ZChemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain10.1038/s41598-017-04198-32045-2322https://doaj.org/article/96230f4ef1f241758be20b03e70e1f372017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04198-3https://doaj.org/toc/2045-2322Abstract We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI. Intrathecal delivery of CXCR4 siRNA or CaMKII inhibitor AIP2 abrogated TCI-induced pain hypersensitivity and TCI-induced increase in p-CaMKII and p-CREB expression. Intrathecal injection of the principal ligand for CXCR4, SDF-1, promoted p-CaMKII and p-CREB expression in naive rats, which was prevented by post-administration of CXCR4 inhibitor Plerixafor or PLC inhibitor U73122. Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.Xue-Ming HuHui ZhangHeng XuHai-Long ZhangLi-Ping ChenWen-Qiang CuiWei YangWen ShenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xue-Ming Hu
Hui Zhang
Heng Xu
Hai-Long Zhang
Li-Ping Chen
Wen-Qiang Cui
Wei Yang
Wen Shen
Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
description Abstract We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI. Intrathecal delivery of CXCR4 siRNA or CaMKII inhibitor AIP2 abrogated TCI-induced pain hypersensitivity and TCI-induced increase in p-CaMKII and p-CREB expression. Intrathecal injection of the principal ligand for CXCR4, SDF-1, promoted p-CaMKII and p-CREB expression in naive rats, which was prevented by post-administration of CXCR4 inhibitor Plerixafor or PLC inhibitor U73122. Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.
format article
author Xue-Ming Hu
Hui Zhang
Heng Xu
Hai-Long Zhang
Li-Ping Chen
Wen-Qiang Cui
Wei Yang
Wen Shen
author_facet Xue-Ming Hu
Hui Zhang
Heng Xu
Hai-Long Zhang
Li-Ping Chen
Wen-Qiang Cui
Wei Yang
Wen Shen
author_sort Xue-Ming Hu
title Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
title_short Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
title_full Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
title_fullStr Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
title_full_unstemmed Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
title_sort chemokine receptor cxcr4 regulates camkii/creb pathway in spinal neurons that underlies cancer-induced bone pain
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/96230f4ef1f241758be20b03e70e1f37
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