Abstract：
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.
摘要：
低镇痛效率限制了镁在镇痛中的使用。这里,我们报道了具有离子电流整流活性的氢化硼（BH）可以显着提高镁的镇痛效率，甚至比吗啡还高.合成的可注射MgB2由与Mg2+交替的六方硼片组成。在病理环境中，而插层的Mg2+将被H+交换，将形成2维硼苯类似物BH片，以通过阳离子-pi相互作用与带电阳离子相互作用，协同导致神经元中钠离子和钾离子电流的一种双向动态调制。通过与释放的Mg2+协调来竞争Ca2+，阈值电位从正常的-35.9mV显著增加到-5.9mV，显著抑制神经元兴奋性，提供有效的镇痛作用。在三种典型的疼痛模型中，包括CFA引起的炎性疼痛，PINP或CCI引起的神经性疼痛，MgB2显示其镇痛效率分别比临床MgSO4高约2.23、3.20和2.0倍。MgB2作为镇痛药物的开发解决了疼痛缓解的未满足的医疗需求，而没有药物耐受性或对阿片类药物成瘾的风险。
