Yi Zhihua, Rao Shenqiang, Ouyang Shuai, Bai Yi, Yang Jinpu, Ma Yucheng, Han Xinyao, Wu Bing, Zou Lifang, Jia Tianyu, Zhao Shanhong, Hu Xiaju, Lei Qiongqiong, Gao Yun, Liu Shuangmei, Xu Hong, Zhang Chunping, Liang Shangdong, Li Guilin
Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Nursing College, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Brain Res Bull. 2017 Apr;130:81-89. doi: 10.1016/j.brainresbull.2017.01.002. Epub 2017 Jan 5.
Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X receptor in gp120-induced neuropathic pain. Our data showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of the P2X mRNA and protein in rats treated with gp120 were higher than those in the control group. The P2X antagonist A317491 decreased mechanical hyperalgesia and thermal hyperalgesia and the up-regulated expression levels of P2X mRNA and protein in rats treated with gp120. A317491 decreased ERK1/2 phosphorylation levels in the gp120-treated rat DRG. In addition, P2X agonist α,β-methylene ATP (α,β-meATP)-activated currents in DRG neurons cultured with gp120 were higher than those in control neurons. The inhibitory effect of A317491 on α,βme-ATP-induced currents in DRG neurons from the gp120-treated neurons was larger than that for control neurons. Molecular docking data showed that A317491 may be acted in the gp120 protein to inhibit the gp120 initiated the P2X activation, decrease the sensitizing DRG primary afferents and reduce the signal transmission of neuropathic pain in gp120-treated rats. Therefore, the inhibition of the P2X receptor in rat DRG neurons relieved gp120-induced mechanical hyperalgesia.
糖蛋白120（gp120）是一种HIV包膜糖蛋白。Gp120可直接刺激初级感觉传入神经元并引起痛觉过敏。背根神经节（DRG）中的P2X受体参与疼痛传递。在本研究中，我们旨在探讨P2X受体在gp120诱导的神经性疼痛中的作用。我们的数据显示，与对照组相比，用gp120处理的大鼠的机械性和热性痛觉过敏增强。用gp120处理的大鼠中P2X mRNA和蛋白的表达水平高于对照组。P2X拮抗剂A317491可减轻用gp120处理的大鼠的机械性痛觉过敏和热性痛觉过敏以及P2X mRNA和蛋白的上调表达水平。A317491降低了用gp120处理的大鼠DRG中ERK1/2的磷酸化水平。此外，在用gp120培养的DRG神经元中，P2X激动剂α,β-亚甲基ATP（α,β-meATP）激活的电流高于对照神经元。A317491对来自用gp120处理的神经元的DRG神经元中α,β-meATP诱导电流的抑制作用大于对照神经元。分子对接数据表明，A317491可能作用于gp120蛋白以抑制gp120引发的P2X激活，降低DRG初级传入神经的敏化并减少用gp120处理的大鼠中神经性疼痛的信号传递。因此，抑制大鼠DRG神经元中的P2X受体可减轻gp120诱导的机械性痛觉过敏。
