Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Curr Neurovasc Res. 2020;17(3):267-274. doi: 10.2174/1567202617666200514113441.
Paclitaxel treatment is a major cause of chemotherapy-induced peripheral neuropathy. The sodium channel Nav1.7 plays a critical role in pain perception. However, whether Nav1.7 in the dorsal root ganglion (DRG) is involved in paclitaxel-induced peripheral neuropathy remains unclear. Thus, our study aimed to evaluate whether Nav1.7 participates in the pathogenesis of paclitaxel-induced neuropathy.
Paclitaxel-induced peripheral neuropathy was generated by intraperitoneal administration of paclitaxel on four alternate days.
The results showed that DRG mRNA and protein expression levels of Nav1.7 were upregulated between days 7 and 21 after the administration of paclitaxel. Besides, paclitaxel upregulated extracellular signal-regulated kinase (ERK1/2) phosphorylation in DRG. Intrathecal injection of U0126 (a MEK inhibitor) blocking ERK1/2 phosphorylation blunted up-regulation of Nav1.7 in the DRG and correspondingly attenuated hyperalgesia.
These results indicated that the sodium channel Nav1.7 in the DRG exerted an important function in paclitaxel-induced neuropathy, which was associated with ERK phosphorylation in neurons.
紫杉醇治疗是化疗引起周围神经病变的主要原因。钠通道 Nav1.7 在疼痛感知中起着关键作用。然而，背根神经节（DRG）中的 Nav1.7 是否参与紫杉醇引起的周围神经病变尚不清楚。因此，我们的研究旨在评估 Nav1.7 是否参与紫杉醇诱导的周围神经病变的发病机制。
紫杉醇诱导的周围神经病通过腹腔内给予紫杉醇四次交替给药产生。
结果表明，紫杉醇给药后第 7 天至第 21 天，DRG 中 Nav1.7 的 mRNA 和蛋白表达水平上调。此外，紫杉醇上调了 DRG 中细胞外信号调节激酶（ERK1/2）的磷酸化。鞘内注射 U0126（MEK 抑制剂）阻断 ERK1/2 磷酸化可减弱 DRG 中 Nav1.7 的上调，并相应减轻痛觉过敏。
这些结果表明，DRG 中的钠离子通道 Nav1.7 在紫杉醇诱导的周围神经病变中发挥了重要作用，这与神经元中 ERK 磷酸化有关。
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