Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats

Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats
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DOI:
10.1016/j.jfma.2013.04.007
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发表时间:
2014-08-01
影响因子:
3.2
通讯作者:
Wong, Chih-Shung
Wong, Chih-Shung
中科院分区:
医学3区
文献类型:
--
作者:
Cherng, Chen-Hwan;Lee, Kwong-Chiu;Wong, Chih-Shung

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背景/目的:在最近的一项研究中,我们发现黄芩苷对角叉菜胶引起的热痛觉过敏表现出有效的镇痛作用。潜在机制可能与抑制炎症介质过度产生有关,包括促炎细胞因子、一氧化氮 (NO) 和前列腺素 E-2 (PGE2)。在本研究中,我们检测了黄芩苷对神经病理性疼痛大鼠脊髓背角吗啡和组蛋白脱乙酰酶1(HDAC1)表达的镇痛作用的影响。方法:通过紧密结扎大鼠左侧L5脊髓神经来诱导神经病理性疼痛。植入鞘内导管用于给药。通过使用哈格里夫斯辐射热装置的足底测试和动态足底麻醉计的冯弗雷测试来评估伤害感受。在伤害感受评估结束时,取出脊髓进行组蛋白乙酰-H3 和 HDAC1 蛋白质印迹分析。 结果:结果显示,在脊髓神经结扎(SNL)的左后肢中观察到痛觉过敏和异常性疼痛;伴随着脊髓背角同侧的组蛋白 H3 脱乙酰化和 HDAC1 过度表达。鞘内注射黄芩苷(10μg)显着减轻异常性疼痛和痛觉过敏,并增强吗啡(15μg)的镇痛作用。此外,黄芩苷逆转SNL大鼠脊髓背角同侧的组蛋白H3乙酰化并抑制HDAC1表达。结论:目前的研究结果表明,黄芩苷可以通过抑制SNL大鼠脊髓背角HDAC1表达并防止组蛋白H3乙酰化来改善神经病理性疼痛。版权所有 (C) 2013,爱思唯尔台湾有限责任公司和台湾医学会。版权所有。
Background/Purpose: In a recent study, we found that baicalin exhibited a potent analgesic effect on carrageenan-evoked thermal hyperalgesia. The underlining mechanisms may be associated with inhibition of inflammatory mediator overproduction, including proinflammatory cytokines, nitric oxide (NO), and prostaglandin E-2 (PGE2). In the present study, we examined the effect of baicalin on the antinociceptive effect of morphine and histone deacetylase 1 (HDAC1) expression in the spinal cord dorsal horn in neuropathic pain rats.Methods: Neuropathic pain was induced by tight ligation of the left L5 spinal nerve of the rats. An intrathecal catheter was implanted for drug administration. Nociception was assessed by using the plantar test with the Hargreaves radiant heat apparatus, and the von Frey test with the dynamic plantar anesthesiometer. Spinal cords were removed for histone acetyl-H3 and HDAC1 western blot analysis at the end of the nociceptive assessment.Results: The results showed that hyperalgesia and allodynia were observed in the spinal nerve ligated (SNL) left hindlimb; it was companied by histone-H3 deacetylation and HDAC1 overexpression on the ipsilateral side of the spinal cord dorsal horn. Intrathecal injection of baicalin (10 mu g) significantly attenuated the allodynia and hyperalgesia, and enhanced the antinociceptive effect of morphine (15 mu g). Moreover, baicalin reversed the histone-H3 acetylation and suppressed HDAC1 expression on the ipsilateral side of the spinal cord dorsal horn of SNL rats.Conclusion: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats. Copyright (C) 2013, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.