title: A Study on the Mechanism of Cinobufagin in the Treatment of Paw Cancer Pain by Modulating Local β -Endorphin Expression In Vivo.
abstract: Background. Cinobufagin has been widely used in the treatment of carcinoma and plays an important role in the relief of cancer pain. But the involved mechanism remains unknown. Aim. To investigate the changes in thermal and mechanical hyperalgesia in paw cancer pain in mice and the action mechanism of cinobufagin using a paw cancer pain model. Methods. 60 female mice were randomly divided into 5 groups: control group, model group, cinobufagin group, cinobufagin +NAL-M group, and morphine group; except ones in control group, mice were inoculated with H22 hepatoma cells in the right hind paw. From the 9th day after inoculation, mice were administrated drug once daily lasting for 8 days. The pain behavior was determined on the 2nd, 4th, 6th, and 8th days before and after administration. On the last day, they were sacrificed. The levels of β -END, CRF, and IL-1 β were analyzed by ELISA; immunohistochemistry was performed to detect the expressions of β -END, POMC, and μ -OR in the tumor and adjacent tissue. Results. The thresholds of thermal pain and mechanical pain were significantly increased by cinobufagin. Moreover, the expressions of β -END, CRF, POMC, and μ -OR were significantly upregulated by cinobufagin. The analgesic effect of cinobufagin was blocked by the peripheral opioid receptor antagonist NAL-M. Conclusions. Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels of β -END and μ -OR in the hind paw tumor and adjacent tissue.
authors.affiliation: College of Medical Science, China Three Gorges University, 8 University Avenue, Yichang, Hubei 443002, China ; Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Yichang, Hubei 443002, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Haibo
authors.initials: H
authors.lastname: He
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Gong
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xueqin
authors.initials: X
authors.lastname: Yu
authors.forename: Ting
authors.initials: T
authors.lastname: Ai
authors.forename: Ling
authors.initials: L
authors.lastname: Zhan