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首页> 外文期刊>The European Journal of Neuroscience >Terminal arbor degeneration--a novel lesion produced by the antineoplastic agent paclitaxel.
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Terminal arbor degeneration--a novel lesion produced by the antineoplastic agent paclitaxel.

机译：末端乔木变性-抗癌药紫杉醇产生的新型病变。

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The antineoplastic agent paclitaxel causes a dose-limiting distal, symmetrical, sensory peripheral neuropathy that is often accompanied by a neuropathic pain syndrome. In a low-dose model of paclitaxel-evoked painful peripheral neuropathy in the rat, we have shown that the drug causes degeneration of intraepidermal nerve fibers (IENFs), i.e. the fibers which give rise to the sensory afferent's terminal receptor arbor. However, we did not find any evidence for axonal degeneration in samples taken at the mid-nerve level. Here we aimed to determine whether the absence of degenerating peripheral nerve axons was due to sampling a level that was too proximal. We used electron microscopy to study the distal-most branches of the nerves innervating the hind paw glabrous skin of normal and paclitaxel-treated rats. We confirmed that we sampled at a time when IENF degeneration was prominent. Because degeneration might be easier to detect with higher paclitaxel doses, we examined a four-fold cumulative dose range (8-32 mg/kg). We found no evidence of degeneration in the superficial subepidermal axon bundles (sSAB) that are located just a few microns below the epidermal basal lamina. Specifically, for all three dose groups there was no change in the number of sSAB per millimeter of epidermal border, no change in the number of axons per sSAB and no change in the diameter of sSAB axons. We conclude that paclitaxel produces a novel type of lesion that is restricted to the afferent axon's terminal arbor; we name this lesion 'terminal arbor degeneration'.
机译：抗癌药紫杉醇引起剂量受限的远端，对称，感觉周围神经病，通常伴有神经性疼痛综合征。在大鼠中紫杉醇引起的疼痛性周围神经病的低剂量模型中，我们已经表明该药物引起表皮内神经纤维（IENFs）变性，即引起感觉传入终末受体心轴的纤维。但是，我们在神经中枢水平采集的样本中未发现任何轴突变性的证据。在这里，我们旨在确定是否没有退化的周围神经轴突是由于采样的水平太近造成的。我们使用电子显微镜研究了正常和紫杉醇处理的大鼠后足无神经支配神经的最远端分支。我们确认我们是在IENF变性明显的时候取样的。由于紫杉醇剂量较高可能更容易检测到变性，因此我们研究了四倍的累积剂量范围（8-32 mg / kg）。我们没有发现表皮下轴突束（sSAB）变性的证据，轴突束位于表皮基底层以下几微米处。具体而言，对于所有三个剂量组，每毫米表皮边界的sSAB数量均无变化，每sSAB的轴突数量均无变化，sSAB轴突的直径均无变化。我们得出的结论是，紫杉醇会产生一种新型病变，仅限于传入轴突的末端乔木。我们将该病变称为“末端乔木变性”。

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