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P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine
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 P2Y...
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Published in: | Purinergic signalling 2018-03, Vol.14 (1), p.47-58 |
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Main Authors: | , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 P2Y
12
receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y
12
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 P2Y
12
receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca
2+
]
i
activated by the P2Y
12
receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y
12
receptor shRNA treatment inhibited 2-MeSADP-induced [Ca
2+
]
i
in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y
12
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 P2Y
12
receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats. |
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ISSN: | 1573-9538 1573-9546 |
DOI: | 10.1007/s11302-017-9594-z |