P2Y₁₂ shRNA treatment relieved HIV gp120-induced neuropathic pain in rats

Human immunodeficiency virus (HIV) envelope glycoprotein (glycoprotein 120, gp120) can induce chronic neuropathic pain by directly stimulating primary sensory afferent neurons. Activation of satellite glial cells (SGCs) in dorsal root ganglia (DRG) plays an important role in the transmission of neuropathic pain. The P2Y₁₂ receptor is expressed in SGCs of DRG. In this study, we investigated the role of the P2Y₁₂ receptor in HIV gp120-induced neuropathic pain. The results showed that peripheral nerve exposure to HIV gp120 increased mechanical and thermal hyperalgesia in gp120-treated model rats. The gp120 treatment increased the expression of P2Y₁₂ mRNA and protein in DRG SGCs. Treatment with P2Y₁₂ short hairpin RNA (shRNA) in DRG SGCs decreased the upregulated expression of P2Y₁₂ mRNA and protein in DRG SGCs as well as relieved mechanical and thermal hyperalgesia in gp120-treated rats. Reduction of P2Y₁₂ receptor decreased co-expression of P2Y₁₂ and glial fibrillary acidic protein (GFAP), expression of GFAP, interleukin (IL)-1β, tumor necrosis factor (TNF)-receptor 1 (TNF-R1), and phosphorylation of Akt (p-Akt) proteins in DRG of gp120-treated rats. Upregulation of GFAP is a marker of SGC activation. Therefore, P2Y₁₂ shRNA treatment decreased HIV gp120-induced mechanical and thermal hyperalgesia in gp120-treated rats.