The synergistic effect of treatment with triptolide and MK-801 in the rat neuropathic pain model.
The synergistic effect of treatment with triptolide and MK-801 in the rat neuropathic pain model.
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雷公藤内酯醇和MK-801治疗大鼠神经病理性疼痛模型的协同作用
DOI：
10.1177/1744806917746564
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Li JL
中科院分区：
文献类型：
--
作者：
Wang J;Qiao Y;Yang RS;Zhang CK;Wu HH;Lin JJ;Zhang T;Chen T;Li YQ;Dong YL;Li JL
雷公藤甲素(Triptolide，T10)是雷公藤中的活性成分，具有较强的抗炎和镇痛作用。此外，非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK-801可降低谷氨酸毒性，对慢性疼痛有显著的镇痛作用。在这项研究中，我们测试了鞘内注射T10和MK-801治疗神经病理性疼痛的可能的协同镇痛能力。脊神经结扎大鼠鞘内注射T10(3、10或30 微克/公斤)、MK-801(10、30或90 微克/公斤)或两者合用。我们发现，单次给药T10产生了缓慢但长期的镇痛作用，而单次给药MK-801产生了快速但短期的效果。二者合用具有明显的协同镇痛作用，以T10与MK-801的1：3比例给药效果最好。此外，应用T10和/或MK-801可显著抑制慢性神经病理性疼痛诱导的脊髓背角小胶质细胞和星形胶质细胞的激活以及STAT3和NR2B的磷酸化。我们的数据表明，T10和MK-801的结合可能是治疗神经病理性疼痛的一种潜在的新策略。
Triptolide (T10), an active component of Tripterygium wilfordii Hook F, is reported to have potent anti-inflammatory and analgesic effects. Additionally, MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, can reduce glutamate toxicity and has a significant analgesic effect on chronic pain. In this study, we tested the possible synergistic analgesic ability by intrathecal administration of T10 and MK-801 for the treatment of neuropathic pain. Single T10 (3, 10, or 30 µg/kg), MK-801 (10, 30, or 90 µg/kg), or a combination of them were intrathecally administrated in rats with spinal nerve ligation. We found that single administration of T10 caused a slow-acting but long-term analgesic effect, while single administration of MK-801 caused a fast-acting but short-term effect. Administration of their combination showed obviously synergic analgesia and the 1:3 ratio of T10 to MK-801 reached the peak effect. Furthermore, application of T10 and/or MK-801 significantly inhibited the activation of microglia and astrocyte and phosphorylation of STAT3 and NR2B in the spinal dorsal horn induced by chronic neuropathic pain. Our data suggest that the combination of T10 and MK-801 may be a potentially novel strategy for treatment of neuropathic pain.
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影响因子：
15.1
作者：
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