LncRNA CRNDE exacerbates neuropathic pain in chronic constriction injury-induced(CCI) rats through regulating miR-146a-5p/WNT5A pathway

ABSTRACT

Neuropathic pain (NP) originating from a dysfunction in the nervous system is often intractable and chronic. Many studies have implicated long noncoding RNAs (lncRNAs) in the physiological and pathological development of NP. The lncRNA colorectal neoplasia differentially expressed gene (CRNDE) has been shown to mediate NP progression. However, further investigations are needed to gain deeper understanding of the specific mechanisms governing CRNDE in NP etiopathology. In this study, we successfully used chronic constrictive injury (CCI)-induced rats to establish an NP model with intrathecal injection, and confirmed the upregulation of CRNDE in CCI-induced rats. Moreover, silencing of CRNDE relieved mechanical allodynia, thermal hyperalgesia, and neuroinflammation in the NP model. Bioinformatics analysis predicted that miR-146a-5p binds to CRNDE. Our findings validated that miR-146a-5p was a target of CRNDE and that the expression of miR-146a-5p was decreased in CCI rats. Furthermore, miR-151A-3p was found to exert a negative regulatory effect on WNT5A. In addition, knockdown of WNT5A alleviated the pain-related behavior and inflammatory response of NP in vivo. Finally, we demonstrated that CRNDE contributed to the progression of CCI-induced NP via competitive binding to miR-146a-5p to upregulate WNT5A. The present study offers novel insights that may be translated into improved therapies for NP.

KEYWORDS:

• Neuropathic pain
• crnde
• miR-146a-5p
• wnt5a
• lncRNA

Acknowledgements

We sincerely appreciate all the participants.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Highlights

1. Silencing CRNDE alleviates the development of NP in vivo.

2. CRNDE serves as a sponge for miR-146a-5p.

3. WNT5A is a target of miR-146a-5p.

4. CRNDE acts as a regulator in NP progression via the miR-146a-5p/WNT5A axis.