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VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA

YuWen Tang, ZhiYou Peng, ShouJun Tao, Jianliang Sun, WenYuan Wang, XueJiao Guo, GongLu Liu, XianZhe Luo, Yuan Chen, Yue Shen, HaiXiang Ma, Peng Xu, Qing Hua Li, HongHai Zhang, View ORCID ProfileZhiYing Feng
doi: https://doi.org/10.1101/655498
YuWen Tang
Department of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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ZhiYou Peng
Department of Anesthesiology and Pain, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
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ShouJun Tao
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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Jianliang Sun
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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WenYuan Wang
Department of Anesthesiology, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
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XueJiao Guo
Department of Anesthesiology and Pain, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
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GongLu Liu
Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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XianZhe Luo
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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Yuan Chen
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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Yue Shen
Department of Anesthesiology, HangZhou First People’s Hospital, Nanjing Medical University, HangZhou, Zhejiang, P.R. China
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HaiXiang Ma
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University
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Peng Xu
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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Qing Hua Li
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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HongHai Zhang
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  • For correspondence: fzy1972@zju.edu.cn
ZhiYing Feng
Department of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, HangZhou, Zhejiang, P.R. China
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  • ORCID record for ZhiYing Feng
  • For correspondence: fzy1972@zju.edu.cn
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Abstract

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating the heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in mediating release of glutamate, contributed to the inflammatory heat. It remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in Inflammatory pain mediated by Cdk5 and the heat hyperalgesia induced by complete Freund’s adjuvant (CFA) can be reversed by roscovitine, a selective inhibitor for Cdk5 through inhibition of VGLUT2 expression. Immunohistochemistry results suggest that when compared with rats in a control group, rats in an experimental group showed significant coexpression of Cdk5/VGLUT2 in small and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA. Moreover, our study revealed that the expression of VGLUT2 protein in DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection. Additionally, p25 but not p35, a activator of Cdk5, protein was significantly increased and reduced by roscovitine. The increased expressions of VGLUT2 protein was significantly reduced by roscovitine as well. Our study showed that VGLUT2/Cdk5 signaling pathway contributed to the inflammatory pain medicated by Cdk5/p25.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 30, 2019.
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VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA
YuWen Tang, ZhiYou Peng, ShouJun Tao, Jianliang Sun, WenYuan Wang, XueJiao Guo, GongLu Liu, XianZhe Luo, Yuan Chen, Yue Shen, HaiXiang Ma, Peng Xu, Qing Hua Li, HongHai Zhang, ZhiYing Feng
bioRxiv 655498; doi: https://doi.org/10.1101/655498
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VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA
YuWen Tang, ZhiYou Peng, ShouJun Tao, Jianliang Sun, WenYuan Wang, XueJiao Guo, GongLu Liu, XianZhe Luo, Yuan Chen, Yue Shen, HaiXiang Ma, Peng Xu, Qing Hua Li, HongHai Zhang, ZhiYing Feng
bioRxiv 655498; doi: https://doi.org/10.1101/655498

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