Upregulation of NGF/TrkA-Related Proteins in Dorsal Root Ganglion of Paclitaxel-Induced Peripheral Neuropathy Animal Model

Yeeun Kim,1,2,* Min-A Je,1,2,* Myeongguk Jeong,1,2 Hyeokjin Kwon,1,2 Aelee Jang,3 Jungho Kim,1,2 Go-Eun Choi1,2 1Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea; 2Next-Generation Industrial Field-Based Specialist Program for Molecular Diagnostics, Brain Busan 21 Plus Project, Graduate School, Catholic University of Pusan, Busan, 46252, Republic of Korea; 3Department of Nursing, University of Ulsan, Ulsan, 44610, Republic of Korea*These authors contributed equally to this workCorrespondence: Go-Eun Choi; Jungho Kim, Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea, Tel +82-51-510-0563 ; +82-51-510-0660, Fax +82-51-510-0568, Email gechoi@cup.ac.kr; jutosa70@cup.ac.krBackground: Paclitaxel (PTX) can induce chemotherapy-induced peripheral neuropathy (CIPN) as a side effect. The aim of this study was to understand the neurochemical changes induced by NGF/TrkA signaling in PTX-induced neuropathic pain.Methods: The PTX-induced CIPN mouse model was evaluated using nerve conduction velocity (NCV) and behavioral tests. Protein expression in mouse DRG was observed by Western blotting and immunohistochemistry. Nerve growth factor (NGF), IL-6, and IL-1β mRNA levels were determined using qRT-PCR by isolating total RNA from whole blood.Results: PTX showed low amplitude and high latency values in NCV in mice, and induced cold allodynia and thermal hyperalgesia in behavioral assessment. Activating transcription factor 3 (ATF3) and MAPK pathway related proteins (ERK1/2), tropomyosin receptor kinase A (TrkA), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) were upregulated 7th and 14th days after 2 mg/kg and 10 mg/kg of PTX administration. Protein kinase C (PKC) was upregulated 7th days after 10 mg/kg PTX treatment and 14th days after 2 mg/kg and 10 mg/kg PTX administration. NGF, IL-6, and IL-1β fold change values also showed a time- and dose-dependent increase.Conclusion: Taken together, our findings may improve our understanding of the nociceptive symptoms associated with PTX-induced neuropathic pain and lead to the development of new treatments for peripheral neuropathy.Keywords: Chemotherapy-induced peripheral neuropathy, paclitaxel, nerve growth factor, tropomyosin receptor kinase A, transient receptor potential vanilloid 1