AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats
AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats
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坐骨神经周围神经施用臭氧激活 AMPK 可减轻 CCI 引起的大鼠神经性疼痛
DOI：
10.1093/jmcb/mjw043
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发表时间：
2017-04-01
影响因子：
5.5
通讯作者：
Liu, Wen-Tao
中科院分区：
文献类型：
--
作者：
Lu, Lijuan;Pan, Cailong;Liu, Wen-Tao
神经病理性疼痛是一种使人虚弱的临床症状，几乎没有有效的治疗方法，因此需要开发新的治疗方法。臭氧被广泛用作治疗许多不同疼痛状况的替代疗法，但确切的机制仍不清楚。在本研究中，我们发现在大鼠坐骨神经慢性压迫损伤模型中，单次坐骨神经周围注射臭氧可减轻机械痛觉异常和热痛敏，并使蛋白激酶Cγ、N-甲基-D-天冬氨酸受体和细胞外信号调节激酶的磷酸化正常化。同时，臭氧显著抑制CCI诱导的脊髓小胶质细胞激活。更重要的是，臭氧的抗伤害性作用依赖于5‘-单磷酸腺苷(AMP)活化的蛋白激酶(AMPK)的激活，这一点在臭氧治疗过程中磷酸化的AMPK水平增加，AMPK拮抗剂在体内和体外取消了臭氧的作用。此外，直接注射AMPK激动剂可复制臭氧对CCI大鼠的抗伤害性作用。总之，我们的观察表明，坐骨神经周围注射臭氧可以激活AMPK，以减轻CCI诱导的神经病理性疼痛。
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain.