Neuropathic pain (NP) is a type of chronic pain affecting 6–8% of human health as no effective drug exists. The purinergic 2X4 receptor (P2X4R) is involved in NP. Neohesperidin (NH) is a dihydroflavonoside compound, which has anti-inflammatory and antioxidative properties. This study aimed to investigate whether NH has an effect on P2X4R-mediated NP induced by chronic constriction injury (CCI) of the sciatic nerve in rats. In this study, the CCI rat model was established to observe the changes of pain behaviors, P2X4R, and satellite glial cells (SGCs) activation in dorsal root ganglion (DRG) after NH treatment by using RT-PCR, immunofluorescence double labeling and Western blotting. Our results showed CCI rats had mechanical and thermal hyperalgesia with an increased level of P2X4R. Furthermore, SGCs were activated as indicated by increased expression of glial fibrillary acidic protein and increased tumor necrosis factor-alpha receptor 1and interleukin-1β. In addition, phosphorylated extracellular regulated protein kinases and interferon regulatory factor 5 in CCI rats increased. After NH treatment in CCI rats, the levels of above protein decreased, and the pain reduced. Overall, NH can markedly alleviate NP by reducing P2X4R expression and SGCs activation in DRG.

神经性疼痛 (NP) 是一种慢性疼痛，影响 6-8% 的人类健康，因为不存在有效的药物。嘌呤能 2X4 受体 (P2X4R) 参与 NP。新橙皮苷 (NH) 是一种二氢黄酮苷化合物，具有抗炎和抗氧化特性。本研究旨在探讨 NH 是否对大鼠坐骨神经慢性压迫性损伤 (CCI) 诱导的 P2X4R 介导的 NP 有影响。本研究建立CCI大鼠模型,采用RT-PCR、免疫荧光双标和Western blotting观察NH处理后背根神经节(DRG)疼痛行为、P2X4R和卫星胶质细胞(SGCs)活化的变化。 . 我们的结果显示 CCI 大鼠有机械和热痛觉过敏，P2X4R 水平升高。此外，如神经胶质纤维酸性蛋白表达增加和肿瘤坏死因子-α 受体 1 和白介素-1β 增加所示，SGC 被激活。此外，CCI 大鼠的磷酸化细胞外调节蛋白激酶和干扰素调节因子 5 增加。CCI大鼠经NH处理后，上述蛋白水平下降，疼痛减轻。总的来说，NH 可以通过减少 DRG 中的 P2X4R 表达和 SGCs 激活来显着减轻 NP。