Cinobufacini protects against paclitaxel-induced peripheral neuropathic pain and suppresses TRPV1 up-regulation and spinal astrocyte activation in rats

被引:45
作者
Ba, Xiyuan [1 ,2 ,3 ]
Wang, Jiali [1 ]
Zhou, Shiyang [1 ]
Luo, Xinxin [1 ]
Peng, Yun [1 ]
Yang, Shimin [1 ]
Hao, Yue [1 ]
Jin, Guangyi [1 ]
机构
[1] Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Peoples R China
[2] Shenzhen Univ, Hlth Sci Ctr, Shenzhen Nanshan Peoples Hosp, Dept Pain Med,Affiliated Hosp 6, Shenzhen 518060, Peoples R China
[3] Shenzhen Univ, Hlth Sci Ctr, Shenzhen Municipal Key Lab Pain Med, Shenzhen Nanshan Peoples Hosp,Affiliated Hosp 6, Shenzhen 518060, Peoples R China
基金
中国国家自然科学基金;
关键词
Cinobufacini; Paclitaxel-induced peripheral neuropathic pain; TRP channels; Astrocyte; Proinflammatory cytokines; POTENTIAL VANILLOID 1; CHEMOTHERAPY; RECEPTOR; CANCER; GEMCITABINE; PREVENTION; INCREASES; INJECTION; HUACHANSU; EFFICACY;
D O I
10.1016/j.biopha.2018.09.018
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Chemotherapy-induced peripheral neuropathic pain is a major limiting factor affecting cancer patients. No effective treatment is currently available. Cinobufacini, an aqueous extract from toad skin, is a widely used anti-cancer drug in China. Clinical evidence has demonstrated the safety and effectiveness of cinobufacini in combination with chemotherapy to promote the therapeutic efficacy while alleviating side effects, especially cancer-related pain symptoms. In this study, the effects of cinobufacini were investigated in a rat model of paclitaxel-induced peripheral neuropathic pain (PIPNP) to better understand and expand its clinical application. A single injection of cinobufacini (2.5 g/kg, i.p.) alleviated pre-established PIPNP, as indicated by decreased mechanical and thermal hypersensitivity compared with paclitaxel-treated rats. Repeated cinobufacini (1.25 and 2.5 g/kg, i.p.), given during the induction of PIPNP, prevented the establishment of paclitaxel-induced mechanical and thermal hypersensitivity. This preventative effect was associated with suppressed paclitaxel-induced TRPV1 up-regulation and spinal astrocyte activation, as well as decreased production of spinal TNF-alpha and IL-1 beta. These findings reveal cinobufacini as a therapeutic potential to treat and prevent paclitaxel-induced peripheral neuropathic pain.
引用
收藏
页码:76 / 84
页数:9
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