P2Y 12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 an
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ORIGINAL ARTICLE
P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine Zhihua Yi 1,2,3 & Lihui Xie 4 & Congfa Zhou 2 & Huilong Yuan 2 & Shuai Ouyang 4 & Zhi Fang 4 & Shanhong Zhao 2 & Tianyu Jia 2 & Lifang Zou 2 & Shouyu Wang 2 & Yun Xue 2 & 2 Bing Wu 2 & Yun Gao 2 & Guilin Li 2 & Shuangmei Liu 2 & Hong Xu 2 & Changshui Xu & Chunping Zhang 2 & Shangdong Liang 1,2
Received: 14 May 2017 / Accepted: 2 November 2017 # Springer Science+Business Media B.V., part of Springer Nature 2017
Abstract 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 HIVgp120+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-MeSADPinduced [Ca2+]i in primary cultured DRG SGCs treated with Zhihua Yi and Lihui Xie contributed equally to this work. * Shangdong Liang [email protected] 1
School of life Sciences of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
2
Department of Physiology, Basic Medical School of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
3
Nursing College, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
4
Undergraduate student of Clinic Medicine School of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
gp120+ddC. Intrathecal treatment with a shRNA against P2Y12 receptor in DRG SGCs reduced the release of proinflammatory 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. Keywords HIV-gp120-associated neuropathic pain . Antiretroviral therapy-associated neuropathic pain . P2Y12 receptor . Dorsal root ganglia . Satellite glial cells
Introduction Infection by the human immunodeficiency virus (HIV) results in progressive failure of the immune system in humans. Distal symmetric polyneuropathy has been recognized as one of the most common neurologic complications of HIV [1–3]. The direct neurotoxicity of HIV and the neurotox
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