Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction
Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction
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DOI：
10.1016/j.pain.2006.01.037
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发表时间：
2006-06-01
期刊：
影响因子：
7.4
通讯作者：
Bennett, GJ
中科院分区：
文献类型：
--
作者：
Flatters, SJL;Bennett, GJ
紫杉醇化疗经常在治疗期间和治疗后持续引起神经性疼痛。造成这种疼痛的机制尚不清楚。使用紫杉醇诱导的疼痛性周围神经病变大鼠模型。我们已经进行了研究以寻找周围神经病理学。紫杉醇诱导的机械性异常性疼痛和机械性痛觉过敏在短暂延迟后明显，在第27天达到峰值，并最终在第155天消退。在第7.27天和第160天灌注紫杉醇和溶剂处理的大鼠。隐神经的一部分进行电子显微镜检查。没有紫杉醇诱导的变性或再生的证据，因为髓鞘结构正常，并且在任何时间点紫杉醇处理均未改变有髓鞘轴突和C-纤维的数量/密度。此外，ATF 3阳性背根神经节细胞的患病率在紫杉醇治疗的动物中是正常的。只有一个例外，在第160天，在有髓鞘的轴突中。在C-纤维和有髓轴突中，总微管密度也不受紫杉醇的影响。与溶媒相比，紫杉醇给药后第7天和第27天C-纤维显著肿胀。最引人注目的发现是在第7天和第27天，紫杉醇治疗神经的C纤维（1.6- 2.3倍）和有髓轴突（2.4- 2.6倍）中非典型（肿胀和空泡化）线粒体的患病率显著增加。与疼痛行为相比，这些线粒体变化在第160天消退。我们的数据不支持紫杉醇引起的疼痛中轴突变性或轴突微管功能障碍的因果关系。而不是.我们的数据表明，紫杉醇诱导的感觉神经轴突线粒体异常有助于紫杉醇诱导的疼痛。(c)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy. we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on days 7.27 and 160. Portions of saphenous nerves were processed for electron microscopy. There was no evidence of paclitaxel-induced degeneration or regeneration as myelin structure was normal and the number/density of myelinated axons and C-fibres was unaltered by paclitaxel treatment at any time point. In addition, the prevalence of ATF3-positive dorsal root ganglia cells was normal in paclitaxel-treated animals. With one exception, at day 160 in myelinated axons. total microtubule densities were also unaffected by paclitaxel both in C-fibres and myelinated axons. C-fibres were significantly swollen following paclitaxel at days 7 and 27 compared to vehicle. The most striking finding was significant increases in the prevalence of atypical (swollen and vacuolated) mitochondria in both C-fibres (1.6- to 2.3-fold) and myelinated axons (2.4- to 2.6-fold) of paclitaxel-treated nerves at days 7 and 27. Comparable to the pain behaviour, these mitochondrial changes had resolved by day 160. Our data do not support a causal role for axonal degeneration or dysfunction of axonal microtubules in paclitaxel-induced pain. Instead. our data suggest that a paclitaxel-induced abnormality in axonal mitochondria of sensory nerves contributes to paclitaxel-induced pain. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.