Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). This study aims to investigate whether botulinum toxin type A (BTX-A) regulates microglial M1/M2 polarization by inhibiting P2X7 expression in a rat model of NP. The BTX-A administration elevated pain threshold, induced microglial polarization toward the M2 phenotype, and decreased P2X7 protein level in a rat model of NP induced by chronic compression injury (CCI). Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model and we demonstrated that BTX-A promoted microglial M2 polarization in LPS-stimulated HAPI microglial cells through suppressing P2X7. Our results indicate that BTX-A promotes microglial M2 polarization and suppresses CCI-induced NP through inhibiting P2X7 receptor. These findings provide new insights into the mechanism of BTX-A in relieving NP.

中文翻译：

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A型肉毒杆菌毒素通过P2X7受体促进小胶质细胞M2极化并抑制慢性缩窄性损伤引起的神经性疼痛

将小胶质细胞极化从促炎 M1 表型转换为抗炎 M2 表型代表了一种新的神经性疼痛 (NP) 治疗策略。本研究旨在研究 A 型肉毒杆菌毒素 (BTX-A) 是否通过抑制 NP 大鼠模型中 P2X7 的表达来调节小胶质细胞 M1/M2 极化。在慢性压缩性损伤 (CCI) 诱导的 NP 大鼠模型中，BTX-A 给药提高了疼痛阈值，诱导小胶质细胞向 M2 表型极化，并降低了 P2X7 蛋白水平。脂多糖 (LPS) 用于激活 HAPI 大鼠小胶质细胞作为体外炎症模型，我们证明 BTX-A 通过抑制 P2X7 促进 LPS 刺激的 HAPI 小胶质细胞中的小胶质细胞 M2 极化。我们的结果表明，BTX-A 通过抑制 P2X7 受体促进小胶质细胞 M2 极化并抑制 CCI 诱导的 NP。这些发现为 BTX-A 缓解 NP 的机制提供了新的见解。