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  2. PI3K/Akt signaling pathway may be involved in MCP-1-induced P2X4R expression in cultured microglia and cancer-induced bone pain rats

PI3K/Akt signaling pathway may be involved in MCP-1-induced P2X4R expression in cultured microglia and cancer-induced bone pain rats

  • Neurosci Lett. 2019 May 14;701:100-105. doi: 10.1016/j.neulet.2019.02.024.
Ying Yan 1 Yongxin Liang 2 Tao Ding 3 Haichen Chu 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266005, China. Electronic address: 1281987612@qq.com.
  • 2 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266005, China. Electronic address: liangzi66@hotmail.com.
  • 3 Department of Articular Surgery, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, Shandong 266000, China. Electronic address: 872649997@qq.com.
  • 4 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266005, China. Electronic address: chiefchu@163.com.
Abstract

P2X4 Receptor (P2X4R), a subtype of P2 purinergic receptors, is an ATP-gated receptor through which activity of spinal microglia instigates pain hypersensitivity in various pain conditions. Accumulating evidence indicates that monocyte chemoattractant protein-1 (MCP-1) plays an important role in chronic pain facilitation, and it could stimulate microglia activation and involve in regulating P2X4R expression. However, the mechanism of MCP-1 in regulating the expression of P2X4R in microglia is poorly understood, and whether MCP-1 can aggravate pain via up-regulating spinal P2X4R expression in Cancer-induced Bone Pain (CIBP) remains unclear. In this study, we observed that Iba-1 and P2X4R expression is increased in microglia treated with MCP-1, and blockade with a selective CCR2 Antagonist RS-504393 suppressed microglia activation and reduced P2X4R expression in cultured microglia. In response to MCP-1, the expression level of p-Akt was also increased and RS-504393 inhibited the increase. Besides, PI3K Inhibitor LY 294002 could attenuate MCP-1-induced P2X4R expression in cultured microglia. MCP-1 was found to be associated with P2X4R expression and mechanical allodynia induced by CIBP in vivo since the expression of MCP-1 was increased in CIBP and RS-504393 alleviated the P2X4R expression and mechanical allodynia in CIBP. Moreover, RS-504393 also reduced the increase of p-Akt induced by CIBP. Inhibition of PI3K/Akt pathway may partly reduce MCP-1/CCR2-induced expression of P2X4R and mechanical allodynia in CIBP rats.

Keywords

Cancer-induced bone pain (CIBP); Microglia; Monocyte chemoattractant protein 1 (MCP-1); P2X4R; PI3K/Akt signaling pathway.

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