title: A317491 relieved HIV gp120-associated neuropathic pain involved in P2X3receptor 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 P2X3receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X3receptor 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 P2X3mRNA and protein in rats treated with gp120 were higher than those in the control group. The P2X3antagonist A317491 decreased mechanical hyperalgesia and thermal hyperalgesia and the up-regulated expression levels of P2X3mRNA and protein in rats treated with gp120. A317491 decreased ERK1/2 phosphorylation levels in the gp120-treated rat DRG. In addition, P2X3agonist 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 P2X3activation, decrease the sensitizing DRG primary afferents and reduce the signal transmission of neuropathic pain in gp120-treated rats. Therefore, the inhibition of the P2X3receptor in rat DRG neurons relieved gp120-induced mechanical hyperalgesia.
authors.affiliation: 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.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Shenqiang
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of the First Clinical, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ouyang
authors.affiliation: Department of the First Clinical, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Queen Mary School, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Queen Mary School, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of the First Clinical, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Jia
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Shanhong
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Nursing College, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Xiaju
authors.initials: X
authors.lastname: Hu
authors.affiliation: Nursing College, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Qiongqiong
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Shuangmei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China. Electronic address: liangsd@hotmail.com.
authors.forename: Shangdong
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China. Electronic address: li.guilin@163.com.
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage* / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D062105:Molecular Docking Simulation; D009437:Neuralgia / Q000139:chemically induced / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold; D010636:Phenols / Q000008:administration & dosage*; D011083:Polycyclic Compounds / Q000008:administration & dosage*; D058911:Purinergic P2X Receptor Agonists / Q000008:administration & dosage; D058920:Purinergic P2X Receptor Antagonists / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*
chemical_list: C470346:A-317491; D015699:HIV Envelope Protein gp120; D010636:Phenols; D011083:Polycyclic Compounds; D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D012333:RNA, Messenger; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate
keywords: A317491; Dorsal root ganglia; HIV gp120-associated neuropathic pain; P2X(3) receptor