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.
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.
Authors: Daniel S Kohane; Sarah E Smith; David N Louis; Gaia Colombo; Peter Ghoroghchian; Nicole G M Hunfeld; Charles B Berde; Robert Langer Journal: Pain Date: 2003-07 Impact factor: 6.961