Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone
Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone
复制标题
钩吻生物碱 koumine 对炎症和神经病理性疼痛模型的影响以及四氢孕酮的可能机制
DOI：
10.1016/j.pbb.2012.02.009
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发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Yu, Chang-Xi
中科院分区：
文献类型：
--
作者：
Xu, Ying;Qiu, Hong-Qiang;Yu, Chang-Xi
钩吻总生物碱粗提物。具有镇痛作用。然而，它的临床实用性受到其狭窄的治疗指数的阻碍。在这里，我们研究了钩吻生物碱单体钩吻碱减轻炎症性疼痛和神经性疼痛的潜力。有趣的是，别孕烯醇酮，一种神经类固醇，似乎介导神经性疼痛的减少。通过醋酸、福尔马林和完全弗氏佐剂（CFA）诱导的小鼠伤害性行为，评价了钩吻素的潜在抗炎镇痛作用。慢性压迫性损伤（CCI）和L5脊神经结扎（L5 SNL），诱导大鼠的热痛觉过敏和机械异常性疼痛，用于测试是否反复治疗钩吻改善神经病理性疼痛。最后，我们用液相色谱-串联质谱法探讨了钩吻素是否改变了CCI神经病大鼠脊髓中神经甾体的水平。钩吻素剂量依赖性地减少醋酸引起的小鼠扭体反应和福尔马林引起的II期舔咬时间。反复施用钩吻素也剂量依赖性地逆转CFA-。CCI和L5 SNL诱导的热痛觉过敏，以及CCI和L5 SNL诱导的大鼠机械异常性疼痛。在CCI诱导的神经病大鼠中，通过反复治疗钩吻素，L5-6脊髓中别孕烯醇酮的水平升高，而非去甲烯醇酮。这些结果表明，钩吻素在炎性和神经性疼痛的啮齿动物行为模型中具有显著的镇痛作用，并且神经性疼痛的减少可能与脊髓中别孕烯醇酮的上调有关。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.