Title:Involvement of the Sodium Channel Nav1.7 in Paclitaxel-induced Peripheral Neuropathy through ERK1/2 Signaling in Rats
Volume: 17
Issue: 3
Author(s): Guang Jie Wang, Xi Zhang, Li-De Huang and Yun Xiao*
Affiliation:
- Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000,China
Keywords:
Extracellular signal-regulated kinase, dorsal root ganglion, hyperalgesia, paclitaxel-induced peripheral neuropathy,
neuron, chemotherapeutic drug.
Abstract:
Background: 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.
Methods: Paclitaxel-induced peripheral neuropathy was generated by intraperitoneal administration
of paclitaxel on four alternate days.
Results: 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.
Conclusion: 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.
