Abstract
The aim of the present study was to observe the changes of TTX-R, Nav1.8, and Nav1.9 Na+ currents in MSU-induced gouty arthritis mice, and to explore the possibility of Nav1.8 and Nav1.9 channels as potential targets for gout pain treatment. Acute gouty arthritis was induced by monosodium urate (MSU) in mice. Swelling degree was evaluated by measuring the circumference of the ankle joint. Mechanical allodynia was assessed by applying the electronic von Frey. Na+ currents were recorded by patch-clamp techniques in acute isolated dorsal root ganglion (DRG) neurons. MSU treatment significantly increased the swelling degree of ankle joint and decreased the mechanical pain threshold. The amplitude of TTX-R Na+ current was significantly increased and reached its peak on the 4th day after injection of MSU. For TTX-R Na+ channel subunits, Nav1.8 current density was significantly increased, but Nav1.9 current density was markedly decreased after MSU treatment. MSU treatment shifted the steady-state activation curves of TTX-R Na+ channel, Nav1.8 and Nav1.9 channels, and the inactivation curves of TTX-R Na+ channel and Nav1.8 channels to the depolarizing direction, but did not affect the inactivation curve of Nav1.9 channel. Compared with the normal group, the recovery of Nav1.8 channel was faster, while that of Nav1.9 channel was slower. The recovery of TTX-R Na+ channel remained unchanged after MSU treatment. Additionally, MSU treatment increased DRG neurons excitability by reducing action potential threshold. Nav1.8 channel, not Nav1.9 channel, may be involved in MSU-induced gout pain by increasing nerve excitability.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Open Fund of Key Laboratory of Medical Electrophysiology, Ministry of Education, Southwest Medical University (No. KeyME-2018-08).
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Jie Qiu performed research and analyzed the data. Xiuqi Xu and Shijia Zhang performed material preparation and data collection. Guang Li designed the study. Guangqin Zhang designed the study and wrote the manuscript. All authors read and approved the final manuscript.
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Qiu, J., Xu, X., Zhang, S. et al. Modulations of Nav1.8 and Nav1.9 Channels in Monosodium Urate–Induced Gouty Arthritis in Mice. Inflammation 44, 1405–1415 (2021). https://doi.org/10.1007/s10753-021-01425-y
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DOI: https://doi.org/10.1007/s10753-021-01425-y