Modulation of tight junction proteins in the perineurium for regional pain control
Modulation of tight junction proteins in the perineurium for regional pain control
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DOI：
10.1111/j.1749-6632.2012.06499.x
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Rittner, H. L.
中科院分区：
文献类型：
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作者：
Hackel, D.;Brack, A.;Rittner, H. L.
周围神经元被神经束膜包围，形成血-神经屏障并保护神经。尽管屏障起到保护作用，但它也阻碍了镇痛药物向周围神经的药物递送。我们先前表明，使用高渗溶液打开屏障有助于药物递送，例如，选择性靶向伤害感受器的亲水性阿片类药物。神经束膜屏障由紧密连接蛋白形成，包括claudin-1、claudin-5和occludin。在病理生理条件下，如神经挤压损伤，神经束膜屏障打开，紧密连接蛋白不再存在。几天后，紧密连接蛋白重新出现，屏障重新密封。类似地，神经束膜注射高渗盐水暂时打开屏障，claudin-1消失，亲水性镇痛药物有效。在未来，这些发现可用于重新密封屏障破坏，并可应用于其他屏障，如血脑屏障或肠粘膜屏障。
Peripheral neurons are surrounded by the perineurium that forms the blood-nerve barrier and protects the nerve. Although the barrier serves as protection, it also hampers drug delivery of analgesic drugs to the peripheral nerve. We previously showed that opening of the barrier using hypertonic solutions facilitates drug delivery, for example, of hydrophilic opioids, which selectively target nociceptors. The perineurial barrier is formed by tight junction proteins, including claudin-1, claudin-5, and occludin. Under pathophysiological conditions such as nerve crush injury, the perineurial barrier is opened and tight junction proteins are no longer present. After several days, tight junction proteins reappear and the barrier reseals. Similarly, perineurial injection of hypertonic saline transiently opens the barrier, claudin-1 disappears, and hydrophilic analgesic drugs are effective. In the future, these findings could be used to reseal the barrier breakdown and could be applied to other barriers like the blood-brain or the intestinal mucosal barrier.