P2Y(12) receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine
P2Y(12) receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine
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卫星胶质细胞中 P2Y(12) 受体上调参与 HIV 糖蛋白 120 和 2',3'-二脱氧胞苷诱导的神经性疼痛
DOI：
10.1007/s11302-017-9594-z
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发表时间：
2018
影响因子：
3.5
通讯作者：
Liang Shangdong
中科院分区：
文献类型：
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作者：
Yi Zhihua;Xie Lihui;Zhou Congfa;Yuan Huilong;Ouyang Shuai;Fang Zhi;Zhao Shanhong;Jia Tianyu;Zou Lifang;Wang Shouyu;Xue Yun;Wu Bing;Gao Yun;Li Guilin;Liu Shuangmei;Xu Hong;Xu Changshui;Zhang Chunping;Liang Shangdong
HIV的直接神经毒性和联合抗逆转录病毒治疗药物的神经毒性都有助于神经性疼痛的发展。背根神经节（DRG）中卫星胶质细胞（SGCs）的激活在机械和热痛觉过敏中起着至关重要的作用。P2 Y12受体在DRG的SGCs中表达，参与痛觉传递。本研究探讨P2 Y12受体在HIV包膜糖蛋白120（gp 120）联合ddC（2′，3 ′-双脱氧胞苷）诱导的神经病理性疼痛中的作用。使用gp 120 + ddC诱导的神经性疼痛的大鼠模型。外周神经暴露于HIV-gp 120 +ddC增加了gp 120 + ddC治疗模型大鼠的机械和热痛觉过敏。gp 120 +ddC处理后，P2 Y12受体mRNA和蛋白表达增加。在原代培养的DRG SGCs中，经gp 120 +ddC处理后，P2 Y12受体激动剂2-（Methylthio）adenosine 5′-diphosphate trisodium salt（2-MeSADP）激活的[Ca 2 +] i水平显著升高。P2 Y12受体shRNA处理抑制2-MeSADP诱导的gp 120 +ddC处理的原代培养DRG SGCs [Ca 2 +] i。鞘内注射针对P2 Y12受体的shRNA可减少gp 120 + ddC处理大鼠DRG中促炎性细胞因子的释放，降低p38 MAPK的磷酸化。因此，下调P2 Y12受体可减轻gp 120 + ddC处理大鼠的机械和热痛觉过敏。
The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y12receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2′,3′-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y12receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca2+]iactivated by the P2Y12receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y12receptor shRNA treatment inhibited 2-MeSADP-induced [Ca2+]iin primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y12receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y12receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.