Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia

The limited analgesic efficiency of magnesium restricts its application in pain management. Here, we report boron hydride (BH) with ion currents rectification activity that can enhance the analgesic efficiency of magnesium without the risks of drug tolerance or addiction. We synthesize MgB₂, comprising hexagonal boron sheets alternating with Mg²⁺. In pathological environment, Mg²⁺ is exchanged by H⁺, forming two-dimensional borophene-analogue BH sheets. BH interacts with the charged cations via cation-pi interaction, leading to dynamic modulation of sodium and potassium ion currents around neurons. Additionally, released Mg²⁺ competes Ca²⁺ to inhibit its influx and neuronal excitation. In vitro cultured dorsal root neurons show a remarkable increase in threshold potential from the normal -35.9 mV to -5.9 mV after the addition of MgB₂, indicating potent analgesic effect. In three typical pain models, including CFA-induced inflammatory pain, CINP- or CCI-induced neuropathic pain, MgB₂ exhibits analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than clinical MgSO₄, respectively, and even about 1.04, 1.66, and 1.95 times higher than morphine, respectively. The development of magnesium based intermetallic compounds holds promise in addressing the non-opioid medical need for pain relief.