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Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway

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Abstract

The role of circular RNAs (circRNAs) in neuropathic pain is linked to the fundamental physiological mechanisms involved. However, the exact function of circRNAs in the context of neuropathic pain is still not fully understood. The functional impact of circGRIN2B on the excitability of dorsal root ganglion (DRG) neurons was investigated using siRNA or overexpression technology in conjunction with fluorescence in situ hybridization and whole-cell patch-clamp technology. The therapeutic efficacy of circGRIN2B in treating neuropathic pain was confirmed by assessing the pain threshold in a chronic constrictive injury (CCI) model. The interaction between circGRIN2B and NF-κB was examined through RNA pulldown, RIP, and mass spectrometry assays. CircGRIN2B knockdown significantly affected the action potential discharge frequency and the sodium-dependent potassium current flux (SLICK) in DRG neurons. Furthermore, knockdown of circGRIN2B dramatically reduced the SLICK channel protein and mRNA expression in vivo and in vitro. Our research confirmed the interaction between circGRIN2B and NF-κB. These findings demonstrated that circGRIN2B promotes the transcription of the SLICK gene by binding to NF-κB. In CCI rat models, the overexpression of circGRIN2B has been shown to hinder the progression of neuropathic pain, particularly by reducing mechanical and thermal hyperalgesia. Additionally, this upregulation significantly diminished the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α in the DRG. Upon reviewing these findings, it was determined that circGRIN2B may mitigate the onset of neuropathic pain by modulating the NF-κB/SLICK pathway.

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Data Availability

The datasets produced and examined throughout the study can be obtained from the corresponding author upon reasonable request.

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Acknowledgements

The authors express their gratitude to the editorial staff of American Journal Experts (AJE) for their valuable contribution in refining and enhancing the quality of the article.

Funding

This research was funded by a Grant (No. 81902252) from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Department of Orthopedics, Zhongda Hospital, Southeast University, Nanjing, China

    Kun Wang, Xiaotao Wu & Lu Mao

  2. Medical School of Southeast University, Nanjing, China

    Kun Wang, Zicong Shen, Xin Peng, Xiaotao Wu & Lu Mao

  3. School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China

    Kun Wang

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  1. Kun Wang
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  2. Zicong Shen
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  3. Xin Peng
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  4. Xiaotao Wu
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  5. Lu Mao
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by KW, ZS, and XP. Financial support and supervision were completed by XW, KW, and LM. The first draft of the manuscript was written by KW, and all the authors read and approved the final manuscript.

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Correspondence to Xiaotao Wu or Lu Mao.

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The authors declare that there are no commercial or financial affiliations that could pose a latent conflict of interest.

Ethical Approval

All surgical procedures and experiments conducted in this study received approval from the Southeast University Ethical Committee (No. 20190218002). These procedures were carried out in strict compliance with the US National Institutes of Health’s Guidelines for the Care and Treatment of Laboratory Animals.

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Wang, K., Shen, Z., Peng, X. et al. Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway. Neuromol Med 26, 12 (2024). https://doi.org/10.1007/s12017-024-08774-5

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