Diyang Ling1, Yan Zhao1, Zhenwu Zhang1, Jiaya Li1, Chunhui Zhu1, Zheyin Wang1. 1. Department of Pain Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology) Shenzhen 518020, Guangdong, China.
Abstract
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-κB and pro-inflammatory factors (TNF-α/IL-1β/IL-6/IL-17a) in rats were detected. Rat left dorsal root ganglion (DRG) cells were extracted and treated with 10, 20 and 30 μmol/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-κB 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-κB 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-κB 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-κB pathway, and the regulation of the PI3K/Akt/NF-κB pathway can improve the therapeutic effect of morphine on chronic tibial cancer pain. AJTR
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-κB and pro-inflammatory factors (TNF-α/IL-1β/IL-6/IL-17a) in rats were detected. Rat left dorsal root ganglion (DRG) cells were extracted and treated with 10, 20 and 30 μmol/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-κB 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-κB 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-κB 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-κB pathway, and the regulation of the PI3K/Akt/NF-κB pathway can improve the therapeutic effect of morphine on chronic tibial cancer pain. AJTR
Authors: Sarah S Shueb; Samuel J Erb; Mary M Lunzer; Rebecca Speltz; Catherine Harding-Rose; Eyup Akgün; Donald A Simone; Philip S Portoghese Journal: Neuropharmacology Date: 2019-07-01 Impact factor: 5.250
Authors: Tisheeka R Graham; Valerie A Odero-Marah; Leland W Chung; Krishna C Agrawal; Rodney Davis; Asim B Abdel-Mageed Journal: Prostate Date: 2009-02-01 Impact factor: 4.104
Authors: Antonello Sica; Beniamino Casale; Maria Teresa Di Dato; Armando Calogero; Alessandro Spada; Caterina Sagnelli; Mario Santagata; Pietro Buonavolontà; Alfonso Fiorelli; Anna Salzano; Concetta Anna Dodaro; Erika Martinelli; Elisabetta Saracco; Teresa Troiani; Dario Tammaro; Fortunato Ciardiello; Alfonso Papa Journal: Open Med (Wars) Date: 2019-10-17