Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

Abstract

Background: Although magnesium ions (Mg2+) are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+). To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans.

Methods: Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short), tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored.

Results: Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling.

Conclusion: Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

Figure 1

Schematic diagram of the graded cooling stimuli. To check changes in spontaneous pain appearing at the injection site, Peltier probe was directly attached to the injection site and cooled the skin in gradual increments.

Figure 2

Time course of changes in effect of magnesium ion on pain and sensations. Fifteen volunteers were intradermally injected with 0.5 M MgSO₄ (black square), 0.05 M MgSO₄ (white square), 0.05 M MgCl₂ (black triangle), or saline (white circle). Each volunteer was injected with three kinds of magnesium solution at intervals of at least one week. Local spontaneous pain (A) was reported by visual analogue scale (VAS), Tactile sensation (B) and pinch pain intensity (D) were reported by a numerical rating score (NRS). When MgSO₄ and MgCl₂ solutions were injected, transient irritating pain and local hypesthesia to mechanical stimuli appeared at the injection site. *p < 0.05 vs. control; **p < 0.01 vs. control, ***p < 0.001 vs. control. As values were similar among these three saline injections, we have put the representative data herein.

Figure 3

Time course of changes in intolerable heat pain evoking temperature after intradermal injection of magnesium solution. Fifteen volunteers were intradermally injected with 0.5 M MgSO₄ (black square), 0.05 M MgSO₄ (white square), 0.05 M MgCl₂ (black triangle), or saline (white circle). Each volunteer was injected with three kinds of magnesium solution at intervals of at least one week. Intolerant heat pain temperature was decreased at least 10 min following local administration of Mg²⁺. *p < 0.05 vs. control; **p < 0.01 vs. control, ***p < 0.001 vs. control. As values were similar among these three saline injections, we have put the representative data herein.

Figure 4

Changes in experienced pain intensity by local cooling. After intradermal administration of 0.5 M MgSO₄, Peltier probe was directly attached to the injection site. Pain intensity was substantially attenuated according to the cooling temperature. (n = 15)