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Papers of the Week

Papers: 2 Feb 2019 - 8 Feb 2019

Animal Studies

2019 Jan-Dec

Mol Pain


Neuroinflammation and central PI3K/Akt/mTOR signal pathway contribute to bone cancer pain.


Zhang J, Wang L, Wang H, Su Z, Pang X
Mol Pain. 2019 Jan-Dec; 15:1744806919830240.
PMID: 30717619.


Pain is one of the most common and distressing symptoms suffered by patients with progression of cancer; however, the mechanisms responsible for hyperalgesia are not well understood. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, in this study we examined the role for pro-inflammatory cytokines (PICs) of the PAG in regulating mechanical and thermal hyperalgesia evoked by bone cancer via PI3K-mTOR signals. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. Western blot analysis and ELISA were used to examine PI3K/Akt/mTOR and PIC receptors and the levels of IL-1β, IL-6 and TNF-α. Protein expression levels of p-PI3K/p-Akt/p-mTOR were amplified in the PAG of bone cancer rats; and blocking PI3K-mTOR pathways in the PAG attenuated hyperalgesia responses. In addition, IL-1β, IL-6 and TNF-α were elevated in the PAG of bone cancer rats and expression of their respective receptors (namely, IL-1R, IL-6R and TNFR subtype TNFR1) was upregulated. Inhibition of IL-1R, IL-6R and TNFR1 alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated PI3K-mTOR. Our data suggest that upregulation of PIC signal in the PAG of cancer rats amplifies PI3K-mTOR signal in this brain region and alters the descending pathways in regulating pain transmission; and this thereby contributes to the development of bone cancer-induced pain.