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Naringenin alleviates bone cancer pain in rats via down-regulating spinal P2X7R /PI3K/AKT signaling: involving suppression in spinal inflammation

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Abstract

Background

Bone cancer pain (BCP) seriously affects patient’s quality of life, which remains a difficult clinical problem, lacking effective drugs for treating it. The inflammation in the spinal cord involves the pathogenesis of BCP. The inhibition of spinal phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or spinal P2X7 receptor (P2X7R) has previously been shown to alleviate BCP. Naringenin (NAR) has analgesic role and anti-inflammatory property.

Objective

The present study investigated the protection of NAR against BCP and explored whether the inhibition of spinal inflammation and the blockade of spinal P2X7R/PI3K/AKT signaling involved in this protection.

Result

NAR significantly alleviated mechanical allodynia (the increase of paw withdrawal threshold in Von Frey test) and thermal hyperalgesia (the increase of paw withdrawal latency in Hargreaves test) in BCP rats. Additionally, NAR inhibited inflammatory cytokines (the reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were measured using Elisa assay) and down-regulated P2X7R/PI3K/AKT signaling (the decreased P2X7R expression, the reduced ratios of phosphorylated (p)-PI3K/PI3K and p-AKT/AKT, which were detected Western blot) in the spinal cord of BCP rats.

Conclusion

NAR alleviated BCP through inhibiting inflammatory cytokines and down-regulating P2X7R/PI3K/AKT signaling in the spinal cord of rats. These findings revealed that NAR, as an effective agent against BCP, may provide an effective approach in the management of bone cancer patients.

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Acknowledgements

This study was supported by the Hunan Provincial Innovation Foundation for Postgraduate (CX2020B633).

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Authors and Affiliations

  1. Department of Orthopaedic, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Jian-Gang Song

  2. Department of Medical Oncology, Hengyang Center Hospital, 12W Yancheng Road, Hengyang, 421001, Hunan, People’s Republic of China

    Lv Liu

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  1. Jian-Gang Song
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  2. Lv Liu
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Contributions

JGS performed the experiments, analyzed the data and writing the manuscript. LL responsible for the experimental design and manuscript revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lv Liu.

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The author Jian-Gang Song declares that he has no conflict of interest and author Lv Liu also declares that she has no conflict of interest.

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The present study was approved by the University Animal Care and Use Committee of Hengyang Center Hospital (Hengyang, China).

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Song, JG., Liu, L. Naringenin alleviates bone cancer pain in rats via down-regulating spinal P2X7R /PI3K/AKT signaling: involving suppression in spinal inflammation. Mol. Cell. Toxicol. 17, 475–484 (2021). https://doi.org/10.1007/s13273-021-00156-3

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  • DOI: https://doi.org/10.1007/s13273-021-00156-3

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