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J Cell Physiol. 2018 Dec;233(12):9620-9628. doi: 10.1002/jcp.26867. Epub 2018 Jun 26.

P2Y12 shRNA treatment decreases SGC activation to relieve diabetic neuropathic pain in type 2 diabetes mellitus rats.

Wang S1,2, Wang Z3, Li L1,2, Zou L1,2, Gong Y4, Jia T1,2, Zhao S1,2, Yuan H1,2, Shi L1,2, Liu S1,2, Wu B1,2, Yi Z1,2, Liu H1,2, Gao Y1,2, Li G1,2, Deussing JM5, Li M6, Zhang C2,7, Liang S1,2.

Author information

1
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi, China.
2
Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang University, Nanchang, Jiangxi, China.
3
Queen Mary School, Medical School of Nanchang University, Nanchang, Jiangxi, China.
4
The Clinical Department, Medical School of Nanchang University, Nanchang, Jiangxi, China.
5
Max Planck Institute of Psychiatry, Munich, Germany.
6
Department of Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
7
Department of Cell Biology, Medical School of Nanchang University, Nanchang, Jiangxi, China.

Abstract

Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus (DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in neuropathic pain through the release of proinflammatory cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our aim was to investigate the role of the P2Y12 receptor on the pathological changes in diabetic neuropathic pain. The present study showed that diabetic neuropathic pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The results showed that the expression levels of P2Y12 messenger RNA (mRNA) and protein in DRG SGCs were increased in DM model rats compared with control rats. Glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-1β) expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA (shRNA) decreased the upregulated expression of P2Y12 mRNA and protein, coexpression of P2Y12 and GFAP, the expression of GFAP, IL-1β, and tumor necrosis factor-receptor 1 in the DRG of DM rats, and relieved mechanical and thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA, the enhancing integrated OPTICAL density (IOD) ratios of p-P38 MAPK to P38 mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA were significantly lower than that in the untreated DM rats. Therefore, P2Y12 shRNA treatment decreased SGC activation to relieve mechanical and thermal hyperalgesia in DM rats.

KEYWORDS:

P2Y12 receptor; diabetic neuropathic pain; dorsal root ganglia (DRG); satellite glial cells (SGCs)

PMID:
29943819
DOI:
10.1002/jcp.26867

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