Terminal arbor degeneration--a novel lesion produced by the antineoplastic agent paclitaxel.
Terminal arbor degeneration--a novel lesion produced by the antineoplastic agent paclitaxel.
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DOI：
10.1111/j.1460-9568.2011.07652.x
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Siau C
中科院分区：
文献类型：
--
作者：
Bennett GJ;Liu GK;Xiao WH;Jin HW;Siau C
抗肿瘤药物紫杉醇导致剂量受限的远端对称性感觉性周围神经病，通常伴有神经病理性疼痛综合征。在小剂量紫杉醇诱导的大鼠痛性周围神经病模型中，我们发现该药可引起表皮内神经纤维(IENF)的变性，即形成感觉传入终末感受器分支的纤维。然而，我们没有在神经中段采集的样本中发现任何轴突变性的证据。在这里，我们的目的是确定周围神经轴突的缺乏是否是由于采样水平太近所致。我们用电子显微镜观察了正常大鼠和紫杉醇处理大鼠的后爪无毛皮肤的神经最远端分支。我们证实，我们的样本是在IENF变性突出的时候进行的。由于较高剂量的紫杉醇可能更容易发现退化，我们检查了四倍的累积剂量范围(8-32 mg/kg)。我们没有发现浅表皮下轴突束(SSAB)变性的证据，SSAB位于表皮基底膜下方几微米处。具体来说，所有三个剂量组的每毫米表皮边缘的SSAB数量没有变化，每个SSAB的轴突数量没有变化，SSAB轴突的直径也没有变化。我们得出结论，紫杉醇产生了一种仅限于传入轴突终枝的新型病变，我们将这种病变命名为末梢变性(TAD)。
The anti-neoplastic 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 arbour. 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 mm 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 (TAD)”.