Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People's Republic of China.
Drug Des Devel Ther. 2024 Jul 22;18:3143-3156. doi: 10.2147/DDDT.S459757. eCollection 2024.
Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.
The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.
Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.
Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.
桑色素可通过抑制神经炎症来缓解长春新碱诱导的神经病理性疼痛。小胶质细胞在疼痛和神经炎症的启动和维持中起重要作用。桑色素是否通过调节小胶质细胞发挥镇痛作用尚不清楚。本研究旨在阐明桑色素对抗神经病理性疼痛的机制，重点是小胶质细胞。
采用热缩足潜伏期和机械缩足阈值作为疼痛行为的测量指标。采用透射电镜观察坐骨神经的组织学异常。坐骨神经功能指数和坐骨神经传导速度作为坐骨神经功能缺损的测量指标。采用 ELISA 检测炎性因子。采用免疫荧光、实时定量 PCR 和 Western blot 检测小胶质细胞 M1/M2 极化标志物和核因子 κB（NF-κB）p65的表达。
桑色素减轻长春新碱诱导的大鼠异常疼痛、坐骨神经损伤和神经炎症反应。此外，桑色素降低 NF-κB P65 和 M1 激活标志物的表达，增加 M2 激活标志物的表达。另外，佛波醇 12-肉豆蔻酸 13-乙酸盐逆转了桑色素对小胶质细胞极化、炎症因子产生和神经病理性疼痛的影响，而氨甲酰吡咯烷二硫代氨基甲酸盐则表现出相反的效果。
我们的结果表明，桑色素通过抑制 NF-κB 信号通路调节 M1/M2 小胶质细胞极化来抑制神经炎症，从而缓解长春新碱诱导的神经病理性疼痛。
