Duloxetine, a Balanced Serotonin-Norepinephrine Reuptake Inhibitor, Improves Painful Chemotherapy-Induced Peripheral Neuropathy by Inhibiting Activation of p38 MAPK and NF-κB

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe, toxic side effect that frequently occurs in anticancer treatment and may result in discontinuation of treatment as well as a serious reduction in life quality. The CIPN incidence rate is as high as 85-90%. Unfortunately, there is current...

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Main Authors: Jing Meng (Author), Qiuyan Zhang (Author), Chao Yang (Author), Lu Xiao (Author), Zhenzhen Xue (Author), Jing Zhu (Author)
Format: Book
Published: Frontiers Media S.A., 2019-04-01T00:00:00Z.
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100 1 0 |a Jing Meng  |e author 
700 1 0 |a Jing Meng  |e author 
700 1 0 |a Qiuyan Zhang  |e author 
700 1 0 |a Chao Yang  |e author 
700 1 0 |a Lu Xiao  |e author 
700 1 0 |a Zhenzhen Xue  |e author 
700 1 0 |a Jing Zhu  |e author 
700 1 0 |a Jing Zhu  |e author 
245 0 0 |a Duloxetine, a Balanced Serotonin-Norepinephrine Reuptake Inhibitor, Improves Painful Chemotherapy-Induced Peripheral Neuropathy by Inhibiting Activation of p38 MAPK and NF-κB 
260 |b Frontiers Media S.A.,   |c 2019-04-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2019.00365 
520 |a Chemotherapy-induced peripheral neuropathy (CIPN) is a severe, toxic side effect that frequently occurs in anticancer treatment and may result in discontinuation of treatment as well as a serious reduction in life quality. The CIPN incidence rate is as high as 85-90%. Unfortunately, there is currently no standard evidence-based CIPN treatment. In several clinical trials, it has been reported that duloxetine can improve CIPN pain induced by oxaliplatin (OXA) and paclitaxel (PTX); thus, The American Society of Clinical Oncology (ASCO) recommends duloxetine as the only potential treatment for CIPN. However, this guidance lacks the support of sufficient evidence. Our study shows that duloxetine markedly reduces neuropathic pain evoked by OXA or PTX. Duloxetine acts by inhibiting the activation of p38 phosphorylation, thus preventing the activation and nuclear translocation of the NF-κB transcription factor, reducing the inflammatory response and inhibiting nerve injury by regulating nerve growth factor (NGF). Furthermore, in this study, it is shown that duloxetine does not affect the antitumor activity of OXA or PTX. This study not only provides biological evidence to support the use of duloxetine as the first standard CIPN drug but will also lead to potential new targets for CIPN drug development. 
546 |a EN 
690 |a chemotherapy-induced peripheral neewopathy (CIPN) 
690 |a duloxetine 
690 |a oxaliplatin (OXA) 
690 |a paclitaxel (PTX) 
690 |a eripheral neuropathic pain 
690 |a dorsal root ganglia (DRG) 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 10 (2019) 
787 0 |n https://www.frontiersin.org/article/10.3389/fphar.2019.00365/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/69f95e7db73d4cfd8d3dd40d2d689ccc  |z Connect to this object online.