The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice.
The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice.
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DOI：
10.1371/journal.pone.0023510
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Koizumi S
中科院分区：
文献类型：
--
作者：
Shibata K;Sugawara T;Fujishita K;Shinozaki Y;Matsukawa T;Suzuki T;Koizumi S
越来越多的证据表明，脊髓胶质细胞，特别是小胶质细胞的激活是神经性疼痛发病的关键事件。然而，抑制小胶质细胞的激活通常是无效的，特别是对于持久的神经性疼痛。到目前为止，神经性疼痛在很大程度上仍然是难治性的，仍然需要一种新的治疗策略。以Seltzer模型小鼠为研究对象，采用免疫组化方法研究了热痛觉过敏和机械性异常痛两种神经性疼痛行为的时间特征，以及脊髓小胶质细胞和星形胶质细胞的形态变化。首先，我们分析了疼痛行为的发展模式，发现疼痛由“早期诱导阶段”和随后的“后期维持阶段”组成。接下来，我们分析了脊髓胶质细胞的时间变化，发现疼痛的诱导和维持阶段分别与小胶质细胞和星形胶质细胞的激活有关。当长期给药一种常用于几种类型的持续性疼痛的日本中草药布氏时，它抑制了疼痛的维持期而不影响诱导期，这与抑制脊髓星形胶质细胞激活一致。这些镇痛作用和对星形胶质细胞活化的抑制作用通过鞘内注射氟柠檬酸盐（星形胶质细胞活化抑制剂）来模拟。最后，我们测试了Bushi对星形胶质细胞激活的直接影响，发现Bushi在体外培养的星形胶质细胞中抑制IL-1β-或il -18诱导的erk1 /2磷酸化，而在体外小胶质细胞中抑制atp诱导的p38-和erk1 /2磷酸化。我们的研究结果表明，脊髓星形胶质细胞的激活与Seltzer模型小鼠神经性疼痛的后期维持阶段有关，因此，布氏液抑制星形胶质细胞的激活可能是治疗神经性疼痛的一种有效的治疗策略。
There is accumulating evidence that the activation of spinal glial cells, especially microglia, is a key event in the pathogenesis of neuropathic pain. However, the inhibition of microglial activation is often ineffective, especially for long-lasting persistent neuropathic pain. So far, neuropathic pain remains largely intractable and a new therapeutic strategy for the pain is still required. Using Seltzer model mice, we investigated the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal hyperalgesia and mechanical allodynia, as well as that of morphological changes in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we analyzed the pattern of progression in the pain behaviors, and found that the pain consisted of an “early induction phase” and subsequent “late maintenance phase”. We next analyzed the temporal changes in spinal glial cells, and found that the induction and the maintenance phase of pain were associated with the activation of microglia and astrocytes, respectively. When Bushi, a Japanese herbal medicine often used for several types of persistent pain, was administered chronically, it inhibited the maintenance phase of pain without affecting the induction phase, which was in accordance with the inhibition of astrocytic activation in the spinal cord. These analgesic effects and the inhibition of astrocytic activation by Bushi were mimicked by the intrathecal injection of fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the direct effect of Bushi on astrocytic activation, and found that Bushi suppressed the IL-1β- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro. Our results indicated that the activation of spinal astrocytes was responsible for the late maintenance phase of neuropathic pain in the Seltzer model mice and, therefore, the inhibition of astrocytic activation by Bushi could be a useful therapeutic strategy for treating neuropathic pain.
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影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
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