VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating 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 modulating release of g...

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Main Authors: Yuwen Tang, Zhiyou Peng, Shoujun Tao, Jianliang Sun, Wenyuan Wang, Xuejiao Guo, Gonglu Liu, Xianzhe Luo, Yuan Chen, Yue Shen, Haixiang Ma, Peng Xu, Qinghua Li, Honghai Zhang, Zhiying Feng
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Pain Research and Management
Online Access:http://dx.doi.org/10.1155/2020/4807674
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author Yuwen Tang
Zhiyou Peng
Shoujun Tao
Jianliang Sun
Wenyuan Wang
Xuejiao Guo
Gonglu Liu
Xianzhe Luo
Yuan Chen
Yue Shen
Haixiang Ma
Peng Xu
Qinghua Li
Honghai Zhang
Zhiying Feng
author_facet Yuwen Tang
Zhiyou Peng
Shoujun Tao
Jianliang Sun
Wenyuan Wang
Xuejiao Guo
Gonglu Liu
Xianzhe Luo
Yuan Chen
Yue Shen
Haixiang Ma
Peng Xu
Qinghua Li
Honghai Zhang
Zhiying Feng
author_sort Yuwen Tang
collection DOAJ
description Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating 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 modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, 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 in the inflammatory pain model induced by complete Freund’s adjuvant (CFA). Our results showed that the 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 was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.
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spelling doaj-art-2d2d3724d7744387a19d8f62216ca08c2025-08-20T02:24:14ZengWileyPain Research and Management1203-67651918-15232020-01-01202010.1155/2020/48076744807674VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s AdjuvantYuwen Tang0Zhiyou Peng1Shoujun Tao2Jianliang Sun3Wenyuan Wang4Xuejiao Guo5Gonglu Liu6Xianzhe Luo7Yuan Chen8Yue Shen9Haixiang Ma10Peng Xu11Qinghua Li12Honghai Zhang13Zhiying Feng14Department of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, ChinaDepartment of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, Hangzhou First People’s Hospital, Nanjing Medical University, HangZhou, Zhejiang, ChinaDepartment of Anesthesiology, The Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Anesthesiology, HangZhou First People’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaVesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating 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 modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, 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 in the inflammatory pain model induced by complete Freund’s adjuvant (CFA). Our results showed that the 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 was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.http://dx.doi.org/10.1155/2020/4807674
spellingShingle Yuwen Tang
Zhiyou Peng
Shoujun Tao
Jianliang Sun
Wenyuan Wang
Xuejiao Guo
Gonglu Liu
Xianzhe Luo
Yuan Chen
Yue Shen
Haixiang Ma
Peng Xu
Qinghua Li
Honghai Zhang
Zhiying Feng
VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
Pain Research and Management
title VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
title_full VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
title_fullStr VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
title_full_unstemmed VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
title_short VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant
title_sort vglut2 cdk5 p25 signaling pathway contributed to inflammatory pain by complete freund s adjuvant
url http://dx.doi.org/10.1155/2020/4807674
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