TY - JOUR
T1 - Magnesium Sulfate Diminishes the Effects of Amide Local Anesthetics in Rat Sciatic-Nerve Block
AU - Hung, Yu Chun
AU - Chen, Chia Ying
AU - Lirk, Philipp
AU - Wang, Chi Fei
AU - Cheng, Jen Kun
AU - Chen, Chien Chuan
AU - Wang, Ging Kuo
AU - Gerner, Peter
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.rapm.2007.03.008
DO - 10.1016/j.rapm.2007.03.008
M3 - Article
C2 - 17720112
AN - SCOPUS:34548039016
SN - 1098-7339
VL - 32
SP - 288
EP - 295
JO - Regional anesthesia and pain medicine
JF - Regional anesthesia and pain medicine
IS - 4
ER -