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, Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000
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.
