Department of Anesthesiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Cell Prolif. 2023 Oct;56(10):e13461. doi: 10.1111/cpr.13461. Epub 2023 Mar 27.
Bone marrow-derived mesenchymal stem cells (BMSCs) show a good property for pain treatment by modulating inflammatory response. However, the underlying therapeutic effect and related mechanism of BMSCs on inflammatory pain remain unclear. Therefore, we explored the function and potential mechanism of BMSCs performing in a complete Freund's adjuvant (CFA)-induced inflammatory pain model in this study. Here, BMSCs were injected into the CFA-treated rats, and we used behavioural tests to evaluate the changes in hypersensitivity. High-throughput sequencing was used to screen out the hub genes. Molecular biology experiments were performed to detect the level of P2X3 or inflammatory mediators in rats and observed the distribution of P2X3 in neural cells. Furthermore, the function of the P2X3 was explored via inhibitor and activator experiments. Finally, we found that BMSCs alleviated hyperalgesia and spinal levels of pro-inflammatory factors in CFA-treated rats. High-throughput sequencing showed that P2X3 and P2X7 were identified as hub genes, and only the expression level of P2X3 was significantly down-regulated after BMSCs treatment. Immunohistochemistry showed that P2X3 mainly colocalized with microglia and astrocytes. The levels of P2X3 and pro-inflammatory factors were all significantly reduced after BMSC injection. Moreover, similar attenuation was found in the CFA-treated rats after injecting the P2X3 inhibitor, and a P2X3 antagonist reversed the attenuation induced by the BMSCs. These findings suggest that BMSCs exerted a therapeutic effect on inflammatory pain by inhibiting the expression of P2X3 and the excessive production of inflammatory mediators was associated with an increased P2X3 level and BMSC therapy reverse these effects.
骨髓间充质干细胞 (BMSCs) 通过调节炎症反应显示出良好的治疗疼痛的特性。然而，BMSCs 对炎症性疼痛的潜在治疗效果和相关机制仍不清楚。因此，我们在这项研究中探索了 BMSCs 在完全弗氏佐剂 (CFA) 诱导的炎症性疼痛模型中的作用及其潜在机制。在这里，将 BMSCs 注射到 CFA 处理的大鼠中，并使用行为学测试来评估过敏反应的变化。高通量测序用于筛选出关键基因。进行分子生物学实验以检测大鼠中 P2X3 或炎症介质的水平，并观察 P2X3 在神经细胞中的分布。此外，通过抑制剂和激活剂实验探索 P2X3 的功能。最后，我们发现 BMSCs 减轻了 CFA 处理的大鼠的痛觉过敏和脊髓中促炎因子的水平。高通量测序显示，P2X3 和 P2X7 被鉴定为关键基因，并且只有 BMSCs 处理后 P2X3 的表达水平明显下调。免疫组织化学显示，P2X3 主要与小胶质细胞和星形胶质细胞共定位。BMSC 注射后 P2X3 和促炎因子的水平均显著降低。此外，在注射 P2X3 抑制剂的 CFA 处理的大鼠中也发现了类似的减弱作用，而 P2X3 拮抗剂逆转了 BMSCs 引起的减弱作用。这些发现表明，BMSCs 通过抑制 P2X3 的表达对炎症性疼痛发挥治疗作用，而过度产生的炎症介质与 P2X3 水平升高有关，BMSC 治疗可逆转这些作用。
