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

紫杉醇诱发周围神经病变动物模型背根神经节中NGF/TrkA相关蛋白的上调

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作者:Yeeun Kim #, Min-A Je #, Myeongguk Jeong, Hyeokjin Kwon, Aelee Jang, Jungho Kim, Go-Eun Choi

Background

Paclitaxel (PTX) can induce chemotherapy-induced peripheral neuropathy (CIPN) as a side effect. The

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.

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.

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