lncRNA MALAT1 contributes to neuropathic pain development through regulating miR-129-5p/HMGB1 axis in a rat model of chronic constriction injury

Abstract

Backgrounds: Mounting studies pay attention to the functional roles of long non-coding RNAs (lncRNAs) in many human diseases including neuropathic pain. LncRNA MALAT1 has been indicated to serve as a critical mediator in neuropathic pain with unclear mechanisms. The present study aims to explore the functional roles of MALAT1 in neuropathic pain progression and the related mechanisms.

Methods: Bilateral sciatic nerves were ligated to induce chronic constriction injury (CCI) in order to establish the neuropathic pain rat model followed by behavioral tests, RT-qPCR, Western blotting, and ELISA. Dual luciferase activity assay was performed to determine the binding effect between MALAT1 or HMGB1 and miR-129-5p.

Results: The mRNA levels of MALAT1 were significantly enhanced in CCI rats. MALAT1 inhibition repressed the development of neuropathic pain and neuroinflammation. Additionally, miR-129-5p was decreased and HMGB1 was increased, both of which could be rectified by MALAT1 inhibition. Meanwhile, MALAT1 targeted miR-129-5p/HMGB1 axis. Finally, miR-129-5p suppression attenuated the inhibitory effect of MALAT1 inhibition on neuropathic pain and neuroinflammation development in CCI rats.

Conclusion: The present study demonstrates that MALAT1 might modulate neuropathic pain via targeting miR-129-5p/HMGB1 axis. These findings may lead to a promising and efficacious clinical approach for the treatment of neuropathic pain.

Keywords:

• Neuropathic pain
• chronic constriction injury
• MALAT1
• miR-129-5p
• HMGB1

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

The study was supported the Project of Hebei Natural Science Foundation (H2017106022).