Human immunodeficiency virus (HIV) envelope glycoprotein (glycoprotein 120, gp120) can induce chronic neuropathic pain by directly stimulating primary sensory afferent neurons. Activation of satellite glial cells (SGCs) in dorsal root ganglia (DRG) plays an important role in the transmission of neuropathic pain. The P2Y12 receptor is expressed in SGCs of DRG. In this study, we investigated the role of the P2Y12 receptor in HIV gp120-induced neuropathic pain. The results showed that peripheral nerve exposure to HIV gp120 increased mechanical and thermal hyperalgesia in gp120-treated model rats. The gp120 treatment increased the expression of P2Y12 mRNA and protein in DRG SGCs. Treatment with P2Y12 short hairpin RNA (shRNA) in DRG SGCs decreased the upregulated expression of P2Y12 mRNA and protein in DRG SGCs as well as relieved mechanical and thermal hyperalgesia in gp120-treated rats. Reduction of P2Y12 receptor decreased co-expression of P2Y12 and glial fibrillary acidic protein (GFAP), expression of GFAP, interleukin (IL)-1β, tumor necrosis factor (TNF)-receptor 1 (TNF-R1), and phosphorylation of Akt (p-Akt) proteins in DRG of gp120-treated rats. Upregulation of GFAP is a marker of SGC activation. Therefore, P2Y12 shRNA treatment decreased HIV gp120-induced mechanical and thermal hyperalgesia in gp120-treated rats.

中文翻译：

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P2Y12 shRNA治疗可减轻HIV gp120诱导的大鼠神经性疼痛。

人类免疫缺陷病毒（HIV）包膜糖蛋白（糖蛋白120，gp120）可以通过直接刺激初级感觉传入神经元来诱发慢性神经性疼痛。背根神经节（DRG）中的卫星神经胶质细胞（SGC）的激活在神经性疼痛的传播中起重要作用。P2Y12受体在DRG的SGC中表达。在这项研究中，我们调查了P2Y12受体在HIV gp120诱导的神经性疼痛中的作用。结果表明，在gp120处理的模型大鼠中，暴露于HIV gp120的周围神经增加了机械和热痛觉过敏。gp120处理可增加DRG SGC中P2Y12 mRNA和蛋白的表达。在DRG SGC中用P2Y12短发夹RNA（shRNA）处理可降低gp120处理的大鼠DRG SGC中P2Y12 mRNA和蛋白的表达上调，并减轻机械和热痛觉过敏。P2Y12受体的减少会降低P2Y12和神经胶质纤维酸性蛋白（GFAP）的共表达，GFAP，白介素（IL）-1β，肿瘤坏死因子（TNF）受体1（TNF-R1）的表达以及Akt（ gp120处理的大鼠的DRG中的p-Akt）蛋白。GFAP的上调是SGC激活的标志。因此，P2Y12 shRNA治疗降低了gp120治疗的大鼠中HIV gp120引起的机械和热痛觉过敏。gp120处理的大鼠的DRG中的肿瘤坏死因子（TNF）受体1（TNF-R1）和Akt（p-Akt）蛋白的磷酸化。GFAP的上调是SGC激活的标志。因此，P2Y12 shRNA治疗降低了gp120治疗的大鼠中HIV gp120引起的机械和热痛觉过敏。gp120处理的大鼠的DRG中的肿瘤坏死因子（TNF）受体1（TNF-R1）和Akt（p-Akt）蛋白的磷酸化。GFAP的上调是SGC激活的标志。因此，P2Y12 shRNA治疗降低了gp120治疗的大鼠中HIV gp120引起的机械和热痛觉过敏。