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首页> 外文期刊>European journal of pain : >Bortezomib-induced painful neuropathy in rats: a behavioral, neurophysiological and pathological study in rats.
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Bortezomib-induced painful neuropathy in rats: a behavioral, neurophysiological and pathological study in rats.

机译：硼替佐米引起的大鼠疼痛性神经病：大鼠的行为，神经生理学和病理学研究。

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Bortezomib is a proteasome inhibitor showing strong antitumor activity against many tumors, primarily multiple myeloma. Bortezomib-induced neuropathic pain is the main side effect and the dose-limiting factor of the drug in clinical practice. In order to obtain a pre-clinical model to reproduce the characteristic pain symptoms in bortezomib-treated patients, we developed an animal model of bortezomib-induced nociceptive sensory neuropathy. In this study, bortezomib (0.15 or 0.20mg/kg) was administered to Wistar rats three times/week for 8 weeks, followed by a 4 week follow-up period. At the end of the treatment period a significant decrease in weight gain was observed in the treated groups vs. controls, and hematological and histopathological parameters were evaluated. After the treatment period, both doses of bortezomib induced a severe reduction in nerve conduction velocity and demonstrated a dose-cumulative effect of the drug. The sensory behavioral assessment showed the onset of mechanical allodynia, while no effect on thermal perception was observed. Sciatic nerves and dorsal root ganglia (DRG) were collected at the end of the 8-week treatment and at the end of the follow-up period. The pathological examination revealed a dose-dependent axonopathy of the unmyelinated fibers in nerves of treated animals. No pathological alteration in most of DRG satellite cells and neurons was observed. Therefore, this animal model may be useful for studying the neurotoxicity and pain onset mechanisms related to bortezomib treatment.
机译：硼替佐米是一种蛋白酶体抑制剂，对许多肿瘤（主要是多发性骨髓瘤）表现出强大的抗肿瘤活性。在临床实践中，硼替佐米引起的神经性疼痛是该药物的主要副作用和剂量限制因素。为了获得能够在硼替佐米治疗的患者中重现特征性疼痛症状的临床前模型，我们开发了一种由硼替佐米引起的伤害性感觉神经病的动物模型。在这项研究中，将硼替佐米（0.15或0.20mg / kg）每周3次给予Wistar大鼠，持续8周，然后进行4周的随访。在治疗期结束时，观察到与对照组相比，治疗组的体重增加显着降低，并且评估了血液学和组织病理学参数。在治疗期之后，两种剂量的硼替佐米均引起神经传导速度的严重降低，并显示出该药物的剂量累积作用。感觉行为评估显示出机械性异常性疼痛的发作，而未观察到对热知觉的影响。在8周治疗结束时和随访期结束时收集坐骨神经和背根神经节（DRG）。病理检查显示治疗动物神经中无髓纤维的剂量依赖性轴突病。在大多数DRG卫星细胞和神经元中未观察到病理改变。因此，该动物模型可用于研究与硼替佐米治疗相关的神经毒性和疼痛发作机制。

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