Modulations of Nav1.8 and Nav1.9 Channels in Monosodium Urate-Induced Gouty Arthritis in Mice.

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.