Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.
Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China.
Neurochem Res. 2023 Oct;48(10):3099-3112. doi: 10.1007/s11064-023-03969-x. Epub 2023 Jun 19.
Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.
嘌呤能受体 P2X4（P2X4R）在神经病理性疼痛中发挥重要作用。然而，其具体机制仍需阐明。肉毒毒素 A 型是由 A 型肉毒梭菌产生的一种神经毒素。本研究发现鞘内注射肉毒毒素 A 型可在慢性缩窄性坐骨神经损伤大鼠模型中产生良好的镇痛效果，并抑制 P2X4R、小胶质细胞和星形胶质细胞的激活。P2X4R 激动剂的给药可上调 P2X4R 的表达并消除鞘内注射肉毒毒素 A 型的镇痛作用。此外，我们发现鞘内注射肉毒毒素 A 型后，大鼠脊髓中的小胶质细胞和星形胶质细胞被重新激活。我们的结果表明，鞘内注射肉毒毒素 A 型通过抑制脊髓中 P2X4R 的激活，在慢性缩窄性坐骨神经损伤大鼠模型中具有镇痛作用。
