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Papers of the Week

2020 Oct 23

Somatosens Mot Res

The hyperpolarization-activated cyclic nucleotide-gated channel currents contribute to oxaliplatin-induced hyperexcitability of DRG neurons.


Yongning Z, Xianguang L, Hengling C, Su C, Fang L, Chenhong L
Somatosens Mot Res. 2020 Oct 23:1-9.
PMID: 33092457.


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.