Involvement of the Sodium Channel Nav1.7 in Paclitaxel-induced Peripheral Neuropathy through ERK1/2 Signaling in Rats.

Abstract

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.