Bharadwaj Vimala N, Meyerowitz Justin, Zou Bende, Klukinov Michael, Yan Ni, Sharma Kaustubh, Clark David J, Xie Xinmin, Yeomans David C
Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
AfaSci Inc., Burlingame, CA 94010, USA.
Pharmaceutics. 2022 May 21;14(5):1105. doi: 10.3390/pharmaceutics14051105.
The intranasal administration of oxytocin (OT) reduces migraine headaches through activation of the oxytocin receptor (OTR). Magnesium ion (Mg concentration is critical to the activation of the OTR, and a low serum Mg concentration is predictive of a migraine headache. We, therefore, examined the functional impact of Mg concentration on OT-OTR binding efficacy using two complimentary bioassays.
Current clamp recordings of rat trigeminal ganglia (TG) neurons measured the impact of Mg on an OT-induced reduction in excitability. In addition, we assessed the impact of Mg on intranasal OT-induced craniofacial analgesia in rats.
While OT alone dose-dependently hyperpolarized TG neurons, decreasing their excitability, the addition of 1.75 mM Mg significantly enhanced this effect. Similarly, while the intranasal application of OT produced dose-dependent craniofacial analgesia, Mg significantly enhanced these effects.
OT efficacy may be limited by low ambient Mg levels. The addition of Mg to OT formulations may improve its efficacy in reducing headache pain as well as for other OT-dependent processes.
经鼻给予催产素(OT)可通过激活催产素受体(OTR)减轻偏头痛。镁离子(Mg)浓度对于OTR的激活至关重要,血清Mg浓度低可预测偏头痛发作。因此,我们使用两种互补的生物测定方法研究了Mg浓度对OT-OTR结合效力的功能影响。
通过对大鼠三叉神经节(TG)神经元进行电流钳记录,测量Mg对OT诱导的兴奋性降低的影响。此外,我们评估了Mg对经鼻给予OT诱导的大鼠颅面部镇痛的影响。
单独使用OT时,TG神经元出现剂量依赖性超极化,兴奋性降低,添加1.75 mM Mg可显著增强此效应。同样,经鼻给予OT可产生剂量依赖性颅面部镇痛,Mg可显著增强这些效应。
OT的效力可能受环境Mg水平低的限制。在OT制剂中添加Mg可能会提高其减轻头痛疼痛以及其他OT依赖性过程的效力。