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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone
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Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone

机译：苦菜碱的生物碱类库米碱对别洛帕那诺酮的炎症和神经性疼痛模型的影响及其可能的机制

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摘要

Crude alkaloidal extraction from Gelsemium elegans Benth. produces analgesic property. However, its clinical utility has been obstructed by its narrow therapeutic index. Here, we investigated the potential of koumine, a monomer of Gelsemium alkaloids, to reduce both inflammatory and neuropathic pain. Interestingly, allopregnanolone, a neurosteroid, appeared to mediate the reduction of neuropathic pain. The potential anti-inflammatory pain effects of koumine were evaluated by acetic acid-, formalin- and complete Freund's adjuvant (CFA) -induced nociceptive behaviors in mice. Chronic constriction injury (CCI) and L5 spinal nerve ligation (L5 SNL), inducing thermal hyperalgesia and mechanical allodynia in rats, were used to test whether repeated treatment of koumine ameliorated neuropathic pain. Finally, we explored if koumine altered the level of neurosteroids in rat spinal cord of CCI neuropathy using liquid chromatography-tandem mass spectrometry. Koumine dose-dependently reduced the acetic acid-induced writhes and formalin-induced licking/biting time of Phase II in mice. Repeated administrations of koumine also dose-dependently reversed the CFA-, CCI- and L5 SNL-induced thermal hyperalgesia, as well as, CCI- and L5 SNL-induced mechanical allodynia in rats. The level of allopregnanolone, but not pregnenolone, in the L5-6 spinal cord was elevated by repeated treatment of koumine in CCI-induced neuropathic rats. These results demonstrate that koumine has a significant analgesic effect in rodent behavioral models of inflammatory and neuropathic pain, and that the reduction in neuropathic pain may be associated with the upregulation of allopregnanolone in the spinal cord.
机译：从线虫Gelthemium Benth粗生物碱提取。产生止痛作用。然而，其狭窄的治疗指数阻碍了其临床应用。在这里，我们研究了苦瓜碱生物碱单体koumine减轻炎症性疼痛和神经性疼痛的潜力。有趣的是，神经固醇阿洛培那那龙似乎可以介导减轻神经性疼痛。通过乙酸，福尔马林和完全弗氏佐剂（CFA）诱导的小鼠伤害性行为评估了口胺的潜在抗炎镇痛作用。慢性收缩性损伤（CCI）和L5脊髓神经结扎（L5 SNL）诱发大鼠热痛觉过敏和机械性异常性疼痛，用于测试可卡因的反复治疗是否可减轻神经性疼痛。最后，我们使用液相色谱-串联质谱法研究了口甲碱是否改变了CCI神经病大鼠脊髓中神经甾体的水平。 Koumine剂量依赖性地减少了II期小鼠的乙酸诱导的扭曲和福尔马林诱导的舔/咬时间。反复施用koumine还可剂量依赖性地逆转CFA，CCI和L5 SNL诱导的大鼠的热痛觉过敏以及CCI和L5 SNL诱导的机械性痛觉过敏。通过反复治疗CCI诱发的神经病大鼠的koumine，可以提高L5-6脊髓中的Allopregnanolone（而非孕烯醇酮）的水平。这些结果表明，孔明在炎性和神经性疼痛的啮齿动物行为模型中具有显着的镇痛作用，并且神经性疼痛的减轻可能与脊髓中Allopregnanolone的上调有关。

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