A317491 relieved HIV gp120-associated neuropathic pain involved in P2X3 receptor in dorsal root ganglia.

Abstract

Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X3 receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X3 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 P2X3 mRNA and protein in rats treated with gp120 were higher than those in the control group. The P2X3 antagonist A317491 decreased mechanical hyperalgesia and thermal hyperalgesia and the up-regulated expression levels of P2X3 mRNA and protein in rats treated with gp120. A317491 decreased ERK1/2 phosphorylation levels in the gp120-treated rat DRG. In addition, P2X3 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 P2X3 activation, decrease the sensitizing DRG primary afferents and reduce the signal transmission of neuropathic pain in gp120-treated rats. Therefore, the inhibition of the P2X3 receptor in rat DRG neurons relieved gp120-induced mechanical hyperalgesia.

• Authors: Zhihua Yi, Shenqiang Rao, Shuai Ouyang, Yi Bai, Jinpu Yang, Yucheng Ma, Xinyao Han, Bing Wu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Xiaju Hu, Qiongqiong Lei, Yun Gao, Shuangmei Liu, Hong Xu, Chunping Zhang, Shangdong Liang, Guilin Li
• Journal: Brain research bulletin (Brain Res Bull) Vol. 130 Pg. 81-89 (04 2017) ISSN: 1873-2747 [Electronic] United States
• PMID: 28065732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• A-317491
• HIV Envelope Protein gp120
• Phenols
• Polycyclic Compounds
• Purinergic P2X Receptor Agonists
• Purinergic P2X Receptor Antagonists
• RNA, Messenger
• Receptors, Purinergic P2X3
• Adenosine Triphosphate
• alpha,beta-methyleneadenosine 5'-triphosphate

Topics

• Adenosine Triphosphate (administration & dosage, analogs & derivatives)
• Animals
• Ganglia, Spinal (drug effects, metabolism)
• HIV Envelope Protein gp120 (administration & dosage, metabolism)
• Hyperalgesia (chemically induced, metabolism)
• MAP Kinase Signaling System
• Male
• Molecular Docking Simulation
• Neuralgia (chemically induced, metabolism)
• Neurons (drug effects, physiology)
• Pain Threshold
• Phenols (administration & dosage)
• Polycyclic Compounds (administration & dosage)
• Purinergic P2X Receptor Agonists (administration & dosage)
• Purinergic P2X Receptor Antagonists (administration & dosage)
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• Receptors, Purinergic P2X3 (metabolism)