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

Abstract:

: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.

journal_name

Front Pharmacol

authors

Meng J,Zhang Q,Yang C,Xiao L,Xue Z,Zhu J

doi

10.3389/fphar.2019.00365

subject

Has Abstract

pub_date

2019-04-09 00:00:00

pages

365

issn

1663-9812

journal_volume

10

pub_type

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