MicroRNA-212-3p Attenuates Neuropathic Pain via Targeting Sodium Voltage-gated Channel Alpha Subunit 3 (NaV 1.3)

Author(s): Yingda Li, Xizhe Zhang, Zhimei Fu*, Qi Zhou.

Journal Name: Current Neurovascular Research

Volume 16 , Issue 5 , 2019

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Abstract:

Purpose: To explore the role and potential mechanism of miR-212-3p in neuropathic pain regulation.

Methods: Adult male rats were used to establish chronic constriction injury (CCI) model to mimic the neuropathic pain. Then, paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWL) were determined. The concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured with enzyme-linked immune sorbent assay (ELISA) kit and the expression of miR-212-3p was measured by real time quantitative PCR (RTqPCR). Besides, miR-212-3p agomir was intrathecally injected into CCI rats and the expression of key apoptotic proteins was determined by western blot. Furthermore, dual-luciferase reporter assay was used to determine the binding of miR-212-3p and 3’ untranslated regions (3’UTR) of NaV1.3 and the expression levels of NaV1.3 were measured by western blot and RT-qPCR.

Results: In the CCI group, the PWT and PWL were significantly decreased and IL-1β, IL-6 and TNF-α were increased. miR-212-3p was decreased in response to CCI. The intrathecal injection of miR-212-3p agomir into CCI rats improved the PWT and PWL, decreased the IL-1β, IL-6 and TNF-α, decreased the expression levels of BCL2 associated X, apoptosis regulator (Bax), cleaved caspase-3 and increased the expression levels of BCL2 apoptosis regulator (Bcl-2). The results of dual--luciferase reporter assay showed that miR-212-3p could directly bind with 3’UTR of NaV1.3. The expression of NaV1.3 was up-regulated in CCI rats who were intrathecally injected with miRctrl, whereas it decreased in CCI rats intrathecally injected with miR-212-3p agomir.

Conclusion: The expression of miR-212a-3p attenuates neuropathic pain by targeting NaV1.3.

Keywords: miR-212-3P, neuropathic pain, CCI rats, NaV1.3, TNF-α, chronic constriction injury.

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VOLUME: 16
ISSUE: 5
Year: 2019
Page: [465 - 472]
Pages: 8
DOI: 10.2174/1567202616666191111104145
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