Humans are likely to experience mechanical allodynia and cold hyperalgesia after oxaliplatin intravenous injection. The mechanism by which oxaliplatin leads to these side effects is unknown. Since the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved in the automatic depolarization of action potentials, we speculated that HCN channels are involved in oxaliplatin-induced hyperalgesia through action potentials. Our results showed that the density of HCN channel currents and the excitability of dorsal root ganglion neurons both increased after oxaliplatin perfusion at the cellular level. The neuronal hyperexcitability could be alleviated by ivabradine. Ivabradine inhibited oxaliplatin-induced mechanical allodynia and cold hyperalgesia at the individual rat level. Oxaliplatin enhanced the function of HCN channels, which in turn promoted the automatic depolarization of action potentials. The acceleration of automatic depolarization excited the neurons and caused more rapid firing of action potentials. Therefore, the HCN channel is a potential therapeutic target for the hyperalgesia induced by oxaliplatin.
基金:
National Natural Science Foundation of China [31870771, 81271234, 81403186, 81771196]; Fundamental Research Funds for the Central Universities; South-Central University for Nationalities [CZY19023]; Natural Science Foundation of Hubei [2020CFA025]
第一作者单位:[1]South Cent Univ Nationalities, Coll Biomed Engn, Lab Membrane Ion Channels & Med, Key Lab Cognit Sci State Ethn Affairs Commiss,Hub, Wuhan, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Zhang Yongning,Lin Xianguang,Chen Hengling,et al.The hyperpolarization-activated cyclic nucleotide-gated channel currents contribute to oxaliplatin-induced hyperexcitability of DRG neurons[J].SOMATOSENSORY AND MOTOR RESEARCH.2021,38(1):11-19.doi:10.1080/08990220.2020.1834376.
APA:
Zhang Yongning,Lin Xianguang,Chen Hengling,Chen Su,Luo Fang&Li Chenhong.(2021).The hyperpolarization-activated cyclic nucleotide-gated channel currents contribute to oxaliplatin-induced hyperexcitability of DRG neurons.SOMATOSENSORY AND MOTOR RESEARCH,38,(1)
MLA:
Zhang Yongning,et al."The hyperpolarization-activated cyclic nucleotide-gated channel currents contribute to oxaliplatin-induced hyperexcitability of DRG neurons".SOMATOSENSORY AND MOTOR RESEARCH 38..1(2021):11-19