P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

Purinergic Signalling

Lihui Xie¹  Congfa Zhou²  Zhihua Yi³  Huilong Yuan⁴ 

[1] Basic Medical School of Nanchang University;Medical School of Nanchang University;School of life Sciences of Nanchang University;Undergraduate student of Clinic Medicine School of Nanchang University

关键词: HIV-gp120-associated neuropathic pain;    Antiretroviral therapy-associated neuropathic pain;    P2Y12 receptor;    Dorsal root ganglia;    Satellite glial cells;   

DOI  :  10.1007/s11302-017-9594-z

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

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 P2Y12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12 receptor 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 P2Y12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca2+]i activated by the P2Y12 receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca2+]i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y12 receptor 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 P2Y12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

【 授权许可】

CC BY