NFAT公司
背根神经节
神经病理性疼痛
奥沙利铂
医学
钙调神经磷酸酶
药理学
内科学
内分泌学
化学
促炎细胞因子
炎症
背
解剖
癌症
移植
结直肠癌
作者
Wan Huang,Jingxiu Huang,Yu Jiang,Xuanwei Huang,Wei Xing,Yaoxuan He,Handong Ouyang
出处
期刊:Anti-cancer Agents in Medicinal Chemistry
[Bentham Science]
日期:2018-12-28
卷期号:18 (8): 1197-1207
被引量:13
标识
DOI:10.2174/1871520618666180525091158
摘要
The aim of this study was to investigate the mechanism of oxaliplatin in the induction of neuropathic pain as a symptom of Chemotherapy-Induced Peripheral Neuropathy (CIPN).The CIPN rat model was induced with a one-time injection of oxaliplatin, and the paw withdrawal response was determined using von Frey filaments. The Paw Withdrawal Threshold (PWT) value was recorded and the Dorsal Horn (DH) and Dorsal Root Ganglion (DRG) tissues were collected. The mRNA and protein levels of Calcineurin (CaN), Nuclear Factor of Activated T cells (NFAT), and other relevant cytokines were determined. CaN and NFAT inhibition reagents, FK506 and 11R-VIVIT, were applied in order to investigate the functions of the CaN/NFAT pathway in the neuropathic pain processes. The levels of the downstream inflammatory cytokines, TNF-α and IL-1β, were assessed by ELISA.The application of oxaliplatin reduced the value of PWT by 4 times on days 7(4±1.33)and 14(5.13±3.07)compared with the control group(14±0.91; 13.67±0.76). After treatment, the CaN mRNA level decreased and that of NFAT increased in DH and DRG tissues (P<0.05). However, treatment with FK506 and 11R-VIVIT decreased the value of PWT that had increased after oxaliplatin treatment. The expression of downstream cytokines related to the CaN/NFAT pathway increased, including CCR2, COX2, p-ERK, and p-P38 (all p<0.05). In addition, when the CaN/NFAT pathway was activated, the concentration of TNFα increased to 40pg/mg in DH tissues and 60pg/mg in DRG tissues compared with the control group, while the concentration of IL-1β increased to over 60pg/mg in DH and DRG tissues.It was the first time to prove that oxaliplatin-induced neuropathic pain was correlated to the activation of the CaN/NFAT pathway in our rat model. This finding can provide a new direction to explore the mechanism of oxaliplatin-induced neuropathic pain.
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