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Updated: May 16, 2025
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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
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Targeting 5-HT to Alleviate Dose-Limiting Neurotoxicity in Nab-Paclitaxel-Based Chemotherapy
Shuangyue Pan1,2, Yu Cai1,2, Ronghui Liu1,2
1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, China.
Neuroscience Bulletin
|May 14, 2025
Summary
Chemotherapy can cause nerve damage, known as chemotherapy-induced peripheral neurotoxicity (CIPN). This study found that serotonin (5-HT) increases nerve damage, but venlafaxine can prevent this side effect during cancer treatment.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Chemotherapy-induced peripheral neurotoxicity (CIPN) is a significant challenge in cancer treatment, often limiting drug dosage.
- The precise mechanisms driving CIPN and effective therapeutic interventions remain largely unknown.
Purpose of the Study:
- To investigate the role of serotonin (5-HT) in nab-paclitaxel-induced neurotoxicity.
- To evaluate the efficacy of venlafaxine in preventing or mitigating CIPN.
Main Methods:
- Metabolomics analysis in cancer patients and mice treated with nab-paclitaxel.
- In vitro studies on enterochromaffin (EC) cells and Schwann cells.
- Assessment of CREB3L3/MMP3/FAS signaling pathways.
- Clinical evaluation of venlafaxine co-administration in patients undergoing nab-paclitaxel chemotherapy.
Main Results:
- Nab-paclitaxel treatment significantly elevated serum serotonin (5-HT) levels.
- Increased 5-HT synthesis was observed in EC cells, and serotonin induced damage in Schwann cells via CREB3L3/MMP3/FAS signaling.
- Venlafaxine protected Schwann cells by inhibiting this signaling pathway.
- Venlafaxine co-administration effectively alleviated CIPN in patients without compromising chemotherapy efficacy.
Conclusions:
- Enterochromaffin cell-derived serotonin (5-HT) is a key mediator of nab-paclitaxel-induced neurotoxicity.
- Venlafaxine is a promising therapeutic agent for preventing chronic cumulative neurotoxicity associated with nab-paclitaxel chemotherapy.
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