NFATc2-dependent epigenetic upregulation of CXCL14 is involved in the development of neuropathic pain induced by paclitaxel.

ABSTRACT:

Background

The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat solid tumor, is painful neuropathy. However, the molecular mechanisms underlying paclitaxel-induced painful neuropathy are largely unclarified.

Methods

Paw withdrawal threshold was measured in the rats following intraperitoneal injection of paclitaxel. The qPCR, western blotting, protein or chromatin immunoprecipitation, ChIP-seq identification of NFATc2 binding sites, and microarray analysis were performed to explore the molecular mechanism.

Results

We found that paclitaxel treatment increased the nuclear expression of NFATc2 in the spinal dorsal horn, and knockdown of NFATc2 with NFATc2 siRNA significantly attenuated the mechanical allodynia induced by paclitaxel.

SUBMITTER: Liu M 

PROVIDER: S-EPMC7570122 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature