Background and Objectives: Magnesium sulfate (MgSO₄) is well known as an antagonist of N-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO₄ combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO₄ could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic-nerve block model. Further, the mechanism of possible synergy between LAs and MgSO₄ was investigated in whole-cell mode patch-clamp experiments.

Methods: Sciatic nerves were exposed to 2%/73.9 mM lidocaine, 0.25%/7.7 mM bupivacaine, and 0.5%/15.4 mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO₄/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO₄ interaction, voltage-dependent inactivation curves were determined in cultured rat GH₃ cells that expressed neuronal Na⁺ channels.

Results: Unexpectedly, the addition of MgSO₄ overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na⁺ channels in the presence of 300 μM lidocaine was almost unchanged by the addition of 10 mM MgSO₄, indicating that MgSO₄ does not affect the potency of lidocaine toward the inactivated Na⁺ channel.

Conclusions: MgSO₄ coadministered with amide-type LAs shortened the duration of sciatic-nerve block in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral-nerve block. The mechanism of this observed antagonism is unclear but appears to be independent of the action of LAs and MgSO₄ at the LA receptor within the Na⁺ channel.