• Wuping Sun, Yue Hao, Rongzhen Li, HoIdy Hiu TingIHTDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong Special Administrative Region., Songbin Wu, Nan Li, Xiyuan Ba, Jie Wang, Donglin Xiong, Changyu Jiang, Lizu Xiao, and Xiaodong Liu.
• Department of Pain Medicine, Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518060, China. Electronic address: wuping.sun@foxmail.com.
• Neuroscience. 2023 Apr 15; 516: 1141-14.

AbstractChemotherapy-induced peripheral neuropathy is one of the most common side effects of anticancer therapy. It is anticipated that chemotherapies with different mechanisms of action may affect somatosensory neurons differently. This study aimed to explore similar and differential etiologies of oxaliplatin- and paclitaxel-induced neuropathy by comparing the transcriptomes of dorsal root ganglia (DRGs). We retrieved our previously published transcriptome data of DRGs extracted from vehicle-, oxaliplatin- and paclitaxel-treated rats (GSE160543), to analyze in parallel the differentially expressed genes (DEGs) and Gene ontology (GO) terms enrichment. We found that both oxaliplatin and paclitaxel treatments consistently produced mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia in rats. Compared to vehicle, 320 and 150 DEGs were identified after oxaliplatin and paclitaxel treatment, respectively. Only 17 DEGs were commonly dysregulated by the two reagents. Activating transcription factor 3 (Atf3), a marker of nerve injury, was elevated only after paclitaxel treatment. GO analysis suggested that paclitaxel treatment was associated with neuronal changes characterized by numerous terms that are related to synaptic transmission, while oxaliplatin was more likely to affect dividing cells (e.g., the glia) and neuroinflammation. Notably, 29 biological processes GO terms were commonly enriched in response to both drugs. However, 28 out of 29 terms were oppositely modulated. This study suggests that distinct mechanisms underly paclitaxel- and oxaliplatin-induced neuropathy. Paclitaxel might directly affect somatosensory neurons while oxaliplatin primarily targets dividing cells and immune cells.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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