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Papers of the Week

Papers: 26 Aug 2023 - 1 Sep 2023


Human Studies, Molecular/Cellular, Neurobiology

Cancer Pain, Musculoskeletal Pain

2023 Aug 31

Sci Rep




Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain.


Fu X, Zhang Y, Zhang R


In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a new Akt inhibitor, was given and the absence of intermediate signal dominated by Akt is found, pain may be relieved by blocking the transmission of pain signal and raising the PWMT. In addition, we also found that GSK690693 inhibited the phosphorylation of Akt protein, resulting in a significant decrease in with-nolysinekinases 1 (WNK1) expression in the spinal cord tissue. In the BCP model, we confirmed that GSK690693 has a relieving effect on BCP, which may play an analgesic effect through PI3K-WNK1 signal pathway. At the same time, there is a close relationship between inflammatory factors and PI3K-WNK1 signal pathway. The PI3K/Akt pathway in the dorsal horn of the mouse spinal cord activates the downstream WNK1 protein, which promotes the release of inflammatory cytokines, which leads to the formation of BCP in mice. Inhibition of Akt can reduce the levels of IL-17 and TNF-α, cut off the downstream WNK1 protein signal receiving pathway, increase the PWMT and relieve BCP in mice. To clarify the analgesic target of BCP, to provide reference and theoretical support for the clinical effective treatment of BCP and the development of new high-efficiency analgesics.