Impact of Magnesium on Oxytocin Receptor Function

SIMPLE SUMMARY: What is already known: Mg(2+) levels modulate the affinity of oxytocin receptors for oxytocin in vitro, low serum Mg(2+) is correlated with migraine headache onset. What this study adds: Electrophysiologic and behavioral assays demonstrate that Mg(2+) increases the efficacy of oxytocin; oxytocin efficacy is limited by Mg(2+) availability. Clinical significance: Modulating Mg(2+) levels may enhance oxytocin efficacy for pain, other uses, and endogenous processes. ABSTRACT: Background and Purpose: The intranasal administration of oxytocin (OT) reduces migraine headaches through activation of the oxytocin receptor (OTR). Magnesium ion (Mg(2+)) concentration is critical to the activation of the OTR, and a low serum Mg(2+) concentration is predictive of a migraine headache. We, therefore, examined the functional impact of Mg(2+) 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 Mg(2+) on an OT-induced reduction in excitability. In addition, we assessed the impact of Mg(2+) 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 Mg(2+) significantly enhanced this effect. Similarly, while the intranasal application of OT produced dose-dependent craniofacial analgesia, Mg(2+) significantly enhanced these effects. Conclusions and Implications: OT efficacy may be limited by low ambient Mg(2+) levels. The addition of Mg(2+) to OT formulations may improve its efficacy in reducing headache pain as well as for other OT-dependent processes.