DNMT3a-triggered downregulation of K_2p 1.1 gene in primary sensory neurons contributes to paclitaxel-induced neuropathic pain.

ABSTRACT: Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K_2p 1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time-dependently downregulates the expression of K _2p 1.1 mRNA and its coding K_2p 1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel-induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced

SUBMITTER: Mao Q 

PROVIDER: S-EPMC6660426 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature