Oxaliplatin treatment changes the function of sensory nerves in rats

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• 作者：Shohei Yamamoto^a ; ^b ; Hideki Ono^b ; ^c ; Kazuhiko Kume^a ; Masahiro Ohsawa^a ; ^b ; ^{ohsawa@phar.nagoya-cu.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Oxaliplatin (L-OHP) ; Neuropathic pain ; Sensory nerve ; Neurometer ; Efferent discharge
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：130
• 期：4
• 页码：189-193
• 全文大小：415 K

文摘

Oxaliplatin (L-OHP) is a platinum-based chemotherapy drug, used in standard treatment of colorectal cancer. L-OHP frequently causes acute peripheral neuropathies. These adverse effects limit cancer therapy with L-OHP. The present study was designed to reveal the changes in sensory nerve function in L-OHP-injected rats. Mechanical static allodynia, dynamic allodynia, and cold allodynia were evaluated using the von Frey test, brush test, and acetone test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. The fifth lumbar ventral root was sectioned to record multi-unit efferent discharges. Single intraperitoneal administration of L-OHP induced mechanical static allodynia, dynamic allodynia, and cold allodynia in Wistar/ST rats. The thresholds for paw withdrawal induced by 2000 Hz (Aβ-fiber) and 5 Hz (C-fiber), but not 250 Hz (Aδ-fiber) sine-wave electrical stimulation were reduced in L-OHP-treated rats. Multi-unit efferent discharges were increased by mechanical stimulation using a von Frey filament applied to the plantar surface of the hindpaw. The discharges during and after stimulation were increased in the L-OHP-treated rats. Cold stimulation, but not brush stimulation, increased the discharges in L-OHP-treated rats. These results suggest that sensitization of Aβ- and C-fibers, but not Aδ-fibers, contributes to the development of L-OHP-induced mechanical and cold allodynia.