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Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain 期刊论文

编号：

99931756-0986-4a24-b078-ef02c634c72c
作者：

Duan, Zongsheng(段宗生)#^[1]Su, Zhenbo(苏振波)#^[2]Wang, Hushan(王虎山)*^[1]Pang, Xiaochuan(庞晓川)*^[3]
语种：

英文
期刊：

MOLECULAR PAIN ISSN：1744-8069 2018 年 14 卷 ; APR 10
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关键词：

Oxaliplatin neuropathic pain mTOR rapamycin pro-inflammation
摘要：

Background: Oxaliplatin is a third-generation chemotherapeutic agent that is commonly used to treat metastatic digestive tumors; however, one of the main limiting complications of oxaliplatin is painful peripheral neuropathy. The purpose of this study was to examine the underlying mechanisms by which mammalian target of rapamycin (mTOR) and its signal are responsible for oxaliplatin-evoked neuropathic pain.
Methods: Neuropathic pain was induced by intraperitoneal injection of oxaliplatin in rats. ELISA and Western blot analysis were used to examine the levels of pro-inflammatory cytokines (including interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha) and the expression of mTOR signal pathway.
Results: Oxaliplatin increased mechanical and cold sensitivity as compared with control animals (P < 0.05 vs. control rats). Oxaliplatin also amplified the expression of p-mTOR and mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 and 4E-binding protein 1 in the lumbar dorsal root ganglion. Blocking mTOR using rapamycin attenuated peripheral painful neuropathy observed in oxaliplatin rats (P < 0.05 vs. vehicle control). This inhibitory effect was accompanied with decreases of IL-1 beta, IL-6, and TNF-alpha. In addition, inhibition of phosphatidylinositide 3-kinase (p-PI3K) attenuated the expression of p-mTOR and the levels of pro-inflammatory cytokines in oxaliplatin rats, and this further attenuated mechanical and cold hypersensitivity.
Conclusions: The data revealed specific signaling pathways leading to oxaliplatin-induced peripheral neuropathic pain, including the activation of PI3K-mTOR and pro-inflammatory cytokine signal. Inhibition of these pathways alleviates neuropathic pain. Targeting one or more of these molecular mediators may present new opportunities for treatment and management of neuropathic pain observed during chemotherapeutic application of oxaliplatin.
推荐引用方式
GB/T 7714：

Duan Zongsheng,Su Zhenbo,Wang Hushan, et al. Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain [J].MOLECULAR PAIN,2018,14.
APA：

Duan Zongsheng,Su Zhenbo,Wang Hushan,Pang Xiaochuan.(2018).Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain .MOLECULAR PAIN,14.
MLA：

Duan Zongsheng, et al. "Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain" .MOLECULAR PAIN 14(2018).
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