Sun Yu, Zhang Kai, Li Chen, Wang QingDong, Zang Rongjia
Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province 154002, P.R. China.
Tuberculosis Department one ward, PLA General Hospital Eighth Medical Center, Beijing 100091, P.R. China.
eNeuro. 2024 Dec 10;11(12). doi: 10.1523/ENEURO.0303-24.2024. Print 2024 Dec.
Neuropathic pain (NP) caused by sciatic nerve injury can significantly impact the quality of life of patients. The M1 phenotype of microglia has been reported to promote the progression of NP. Procaine is a lipid-soluble local anesthetic drug that exerts narcotic analgesic effects. Nevertheless, the detailed effect of procaine in NP is not clear. In order to explore the role of procaine in the polarization of NP microglia, HAPI cells were exposed to LPS to polarize into M1 type. In addition, the number of the M1 phenotype of HAPI cells was assessed using flow cytometry. The binding site between CCL5 and STAT3 was explored using the dual luciferase assay. Furthermore, in vivo experiments were applied for testing the impact of procaine on NP. LPS significantly inhibited HAPI cell viability, which was reversed by procaine. Consistently, procaine alleviated LPS-induced upregulation of inflammatory factors. Additionally, it significantly inhibited HAPI cell M1 polarization induced by LPS. Meanwhile, overexpression of STAT3 was able to promote HAPI cells M1 polarization through binding with the CCL5 promoter region and activating the PI3K/Akt signaling. Procaine could alleviate the painful behavior of complete Freund's adjuvant (CFA) rats by modulating the STAT3/CCL5 axis and inhibiting microglia M1 polarization. In conclusion, procaine alleviated the painful behavior of CFA rats via regulating the STAT3/CCL5 axis and inhibiting microglia M1 polarization. Hence, the research might provide a novel agent for NP treatment.
坐骨神经损伤引起的神经性疼痛（NP）会显著影响患者的生活质量。据报道，小胶质细胞的M1表型会促进NP的进展。普鲁卡因是一种脂溶性局部麻醉药，具有麻醉镇痛作用。然而，普鲁卡因在NP中的具体作用尚不清楚。为了探究普鲁卡因在NP小胶质细胞极化中的作用，将HAPI细胞暴露于脂多糖（LPS）中使其极化为M1型。此外，使用流式细胞术评估HAPI细胞M1表型的数量。采用双荧光素酶报告基因检测法探究CCL5与信号转导和转录激活因子3（STAT3）之间的结合位点。此外，进行体内实验以测试普鲁卡因对NP的影响。LPS显著抑制HAPI细胞活力，而普鲁卡因可逆转这一作用。同样，普鲁卡因可减轻LPS诱导的炎症因子上调。此外，它还能显著抑制LPS诱导的HAPI细胞M1极化。同时，STAT3的过表达能够通过与CCL5启动子区域结合并激活磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路来促进HAPI细胞的M1极化。普鲁卡因可通过调节STAT3/CCL5轴并抑制小胶质细胞M1极化来减轻完全弗氏佐剂（CFA）大鼠的疼痛行为。综上所述，普鲁卡因通过调节STAT3/CCL5轴并抑制小胶质细胞M1极化来减轻CFA大鼠的疼痛行为。因此，该研究可能为NP治疗提供一种新型药物。
