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KMID : 1034820210170040475
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Molecular & Cellular Toxicology
2021 Volume.17 No. 4 p.475 ~ p.484
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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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Song Jian-Gang
Liu Lv
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Abstract
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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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KEYWORD
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Bone cancer pain, Naringenin, P2X7 receptor, PI3K/AKT signaling, Inflammatory cytokines
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