Impact of Magnesium on Oxytocin Receptor Function

Simple Summary What is already known: Mg2+ levels modulate the affinity of oxytocin receptors for oxytocin in vitro, low serum Mg2+ is correlated with migraine headache onset. What this study adds: Electrophysiologic and behavioral assays demonstrate that Mg2+ increases the efficacy of oxytocin; oxytocin efficacy is limited by Mg2+ availability. Clinical significance: Modulating Mg2+ levels may enhance oxytocin efficacy for pain, other uses, and endogenous processes. Background and Purpose: The intranasal administration of oxytocin (OT) reduces migraine headaches through activation of the oxytocin receptor (OTR). Magnesium ion (Mg2+) concentration is critical to the activation of the OTR, and a low serum Mg2+ concentration is predictive of a migraine headache. We, therefore, examined the functional impact of Mg2+ concentration on OT-OTR binding efficacy using two complimentary bioassays. Experimental Approach: Current clamp recordings of rat trigeminal ganglia (TG) neurons measured the impact of Mg2+ on an OT-induced reduction in excitability. In addition, we assessed the impact of Mg2+ on intranasal OT-induced craniofacial analgesia in rats. Key Results: While OT alone dose-dependently hyperpolarized TG neurons, decreasing their excitability, the addition of 1.75 mM Mg2+ significantly enhanced this effect. Similarly, while the intranasal application of OT produced dose-dependent craniofacial analgesia, Mg2+ significantly enhanced these effects. Conclusions and Implications: OT efficacy may be limited by low ambient Mg2+ levels. The addition of Mg2+ to OT formulations may improve its efficacy in reducing headache pain as well as for other OT-dependent processes.