Morphine inhibits the promotion of inflammatory microenvironment on chronic tibial cancer pain through the PI3K-Akt-NF-kappa B pathway

Ling, Diyang; Zhao, Yan; Zhang, Zhenwu; Li, Jiaya; Zhu, Chunhui; Wang, Zheyin

2020

American Journal of Translational Research   影响因子和分区

1943-8141

Purpose: Inflammatory microenvironment is critical in the transmission of advanced cancer pain. This paper will study how morphine ameliorates advanced cancer pain through inflammatory microenvironment. Methods: Fifty female healthy rats were selected and divided into control group, sham group, model group, morphine group and morphine + 740YP group by random number table. At the left tibia, rats in the model, morphine and morphine + 740YP groups received Walker256 cells injection, while those in the sham group received an equal amount of Hank solution. The control group received no treatment. After modeling, the rats' spontaneous pain behavior, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured and statistically analyzed. The protein levels of PI3K, Akt, NF-kappa B and pro-inflammatory factors (TNF-alpha/IL-1 beta/IL-6/IL-17a) in rats were detected. Rat left dorsal root ganglion (DRG) cells were extracted and treated with 10, 20 and 30 mu mol/L morphine to observe their effects on the cells. Results: Compared with the control group, the model group presented increased spontaneous pain behavior and PWTL, decreased PWMT, and reduced mechanical pain threshold, as well as enhanced levels of PI3K, Akt, NF-kappa B and pro-inflammatory factors in vivo as compared to the control group. While the morphine group showed less spontaneous pain behavior and PWTL, increased PWMT, and down-regulated PI3K, Akt, NF-kappa B and pro-inflammatory factors in vivo in comparison with the model group. After morphine treatment, the apoptosis of DRG cells decreased and the cell activity increased, while PI3K, Akt, NF-kappa B and pro-inflammatory factors levels decreased. Morphine affected DRG cells in a dose-dependent manner. Up regulation of PI3K could counteract the inhibitory effect of morphine on chronic tibial cancer pain. Conclusions: Morphine inhibits the promotion of inflammatory microenvironment on chronic tibial cancer pain via the PI3K/Akt/NF-kappa B pathway, and the regulation of the PI3K/Akt/NF-kappa B pathway can improve the therapeutic effect of morphine on chronic tibial cancer pain.

Chronic tibia cancer pain morphine PI3K-Akt-NF-kappa B pathway inflammation microenvironment

SCI

英语

第一 ; 通讯

Oncology ; Research & Experimental Medicine

Oncology ; Medicine, Research & Experimental

WOS:000583894800070

E-CENTURY PUBLISHING CORP

Web of Science

Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Clin Med Coll 2,Dept Pain Med,Shenzhen Peoples Ho, Shenzhen 518020, Guangdong, Peoples R China

Ling, Diyang,Zhao, Yan,Zhang, Zhenwu,et al. Morphine inhibits the promotion of inflammatory microenvironment on chronic tibial cancer pain through the PI3K-Akt-NF-kappa B pathway[J]. American Journal of Translational Research,2020,12(10):6868-6878.

Ling, Diyang,Zhao, Yan,Zhang, Zhenwu,Li, Jiaya,Zhu, Chunhui,&Wang, Zheyin.(2020).Morphine inhibits the promotion of inflammatory microenvironment on chronic tibial cancer pain through the PI3K-Akt-NF-kappa B pathway.American Journal of Translational Research,12(10),6868-6878.

Ling, Diyang,et al."Morphine inhibits the promotion of inflammatory microenvironment on chronic tibial cancer pain through the PI3K-Akt-NF-kappa B pathway".American Journal of Translational Research 12.10(2020):6868-6878.