Magnesium is being investigated in various clinical conditions and has shown to be effective in some chronic pain models. However, it is not clear if oral magnesium use affects pain perception in acute pain. TLR4's (toll-like receptor) role in pain perception has emerged through its role in immune pathways and ion channels. The aim of this study is to investigate the effect of a single oral dose of magnesium citrate on pain conduction and whether with magnesium, the expression of TLR4 changes in the acute phase. Following a single dose of 66-mg/kg magnesium citrate administration to male Balb-c mice, pain perception (via hot-plate test), motor conduction (via electrophysiological recording, forelimb grip strength, rotarod and open-field tests), and emotional state (via elevated plus maze and forced swim test) were evaluated. In behavioral experiments, the control group was compared with applied magnesium for three different time groups (4, 8, 24 h). TLR4 expression was measured in four groups: control, magnesium (Mg), hot plate (HP), and Mg + HP. Hot plate latency was prolonged in the magnesium group (p < 0.0001) and electrophysiological recordings (p < 0.001) and forelimb grip strength measurement (p < 0.001) determined motor latency. Compared with the untreated hot plate group, TLR4 levels was lower in the brain (p = 0.023) and higher in the sciatic nerve (p = 0.001) in the magnesium-treated hot plate group. Consequently, the study indicated a single dose of magnesium citrate appeared to cause weakening in the transmission and perception of nociceptive pain. TLR4 may act as a regulator in magnesium's effects on pain perception.
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