Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block

Abstract

Background and objectives: Magnesium sulfate (MgSO(4)) 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 MgSO(4) combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO(4) 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 MgSO(4) 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% MgSO(4)/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO(4) interaction, voltage-dependent inactivation curves were determined in cultured rat GH(3) cells that expressed neuronal Na(+) channels.

Results: Unexpectedly, the addition of MgSO(4) overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na(+) channels in the presence of 300 muM lidocaine was almost unchanged by the addition of 10 mM MgSO(4), indicating that MgSO(4) does not affect the potency of lidocaine toward the inactivated Na(+) channel.

Conclusions: MgSO(4) 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 MgSO(4) at the LA receptor within the Na(+) channel.

Fig. 1

Rat sciatic nerve blockade by 2% lidocaine combined with 0%, 1.25%, 2.5%, or 5% MgSO₄ (n = 8/group). Time courses of proprioceptive, motor, and nociceptive blockade by lidocaine combined with MgSO₄ at various concentrations are shown in (A), (C), and (E), respectively. A score of 0 indicates no block or baseline, and a score of 3 indicates complete blockade. The complete blockade time (CBT) and complete recovery time (CRT) in minutes for proprioceptive, motor, and nociceptive function are shown in (B), (D), and (F). Data are presented as mean ± SEM. * P < 0.004 (lidocaine alone vs. lidocaine with MgSO₄ added).

Fig. 2

Rat sciatic nerve blockade by 0.25% bupivacaine combined with 0%, 1.25%, 2.5%, or 5% MgSO₄ (n = 8/group). Time courses of block (A), (C), and (E), CBT and CRT (B), (D), and (F), as outlined in figure 1. Data are presented as mean ± SEM. * P < 0.004 (bupivacaine alone vs. bupivacaine with MgSO₄ added).

Fig. 3

Rat sciatic nerve blockade by 0.5% ropivacaine combined with 0%, 1.25%, 2.5%, or 5% MgSO₄ (n = 8/group). Time courses of block (A), (C), and (E), CBT and CRT (B), (D), and (F), as outlined in figure 1. Data are presented as mean ± SEM. * P < 0.004 (ropivacaine alone vs. ropivacaine with MgSO₄ added).

Fig. 4

Na⁺ current inhibition by lidocaine alone, lidocaine combined with MgSO₄, and MgSO₄ alone (n = 5 cells/group; data are presented as mean ± SEM). The respective pulse protocol is inserted above the representative tracings. Conditioning prepulses ranging in amplitude from -160 to -15 mV were applied. Na⁺ currents were evoked by the delivery of the test pulse to -30 mV. Pulse protocol is inserted on the top of the figure. (A) Normalized Na⁺ current in the absence (control) or presence of 300 μM lidocaine was plotted against conditioning prepulse potential. Data were fitted well with a Boltzmann function. The average V_0.5 value (50% availabilities) and K_E (a slope factor) values for the fitted Boltzmann functions were -63.8 ± 0.14 mV and 6.3 ± 0.13 for control and -68.7 ± 0.24 mV and 7.0 ± 0.21 for lidocaine, respectively. (B) Voltage-dependent block of Na⁺ channels by 10 mM MgSO₄ alone. No change in inactivation occurred. The average V_0.5 value (50% availabilities) and K_E (a slope factor) values for the fitted Boltzmann functions were -61.5 ± 0.23 mV and 5.9 ± 0.2 for control and -62.0 ± 0.13 mV and 6.1 ± 0,13 for MgSO₄, respectively. (C) Voltage-dependent block of Na+ channels by 300 μM lidocaine combined with 10 mM MgSO₄. The average V_0.5 value (50% availabilities) and K_E (a slope factor) values for the fitted Boltzmann functions were -59.8 ± 0.16 mV and 5.8 ± 0.1 for control and lidocaine combined with MgSO₄, respectively, and -65.2 ± 0.14 mV and 6.2 ± 0.1, respectively.