脊髓小胶质细胞 P2X7 受体参与大鼠吗啡镇痛耐受的产生。
Involvement of spinal microglial P2X7 receptor in generation of tolerance to morphine analgesia in rats.
机构信息
Unit of Pain Research, Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
出版信息
J Neurosci. 2010 Jun 9;30(23):8042-7. doi: 10.1523/JNEUROSCI.5377-09.2010.
Abstract
Morphine loses analgesic potency after repeated administration. The underlying mechanism is not fully understood. Glia are thought to be involved in morphine tolerance, and P2X(7) purinergic receptor (P2X(7)R) has been implicated in neuron-glia communication and chronic pain. The present study demonstrated that P2X(7)R immunoreactivity was colocalized with the microglial marker OX42, but not the astrocytic marker GFAP, in the spinal cord. The protein level of spinal P2X(7)R was upregulated after chronic exposure to morphine. Intrathecal administration of Brilliant Blue G (BBG), a selective P2X(7)R inhibitor, significantly attenuated the loss of morphine analgesic potency, P2X(7)R upregulation, and microglial activation. Furthermore, RNA interference targeting the spinal P2X(7)R exhibited a similar tolerance-attenuating effect. Once morphine analgesic tolerance is established, it was no longer affected by intrathecal BBG. Together, our results suggest that spinal P2X(7)R is involved in the induction but not maintenance of morphine tolerance.
摘要
吗啡反复给药后会失去镇痛效力。其潜在机制尚未完全阐明。小胶质细胞被认为与吗啡耐受有关，而 P2X(7)嘌呤能受体（P2X(7)R）参与神经元-神经胶质细胞通讯和慢性疼痛。本研究表明，脊髓 P2X(7)R 免疫反应性与小胶质细胞标志物 OX42 共定位，但与星形胶质细胞标志物 GFAP 不共定位。慢性暴露于吗啡后，脊髓 P2X(7)R 蛋白水平上调。鞘内给予 Brilliant Blue G (BBG)，一种选择性 P2X(7)R 抑制剂，可显著减轻吗啡镇痛效力的丧失、P2X(7)R 上调和小胶质细胞激活。此外，针对脊髓 P2X(7)R 的 RNA 干扰也表现出类似的耐受减轻作用。一旦吗啡镇痛耐受建立，鞘内 BBG 不再影响其作用。综上所述，我们的结果表明，脊髓 P2X(7)R 参与吗啡耐受的诱导，但不参与其维持。
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