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Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans

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@article{d31b1d792197491f89728ad95ebf6e95,
title = "Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans",
abstract = "The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.",
author = "Mihai Moldovan and Lange, {Kai Henrik Wiborg} and Aachmann-Andersen, {Niels Jacob} and Kj{\ae}r, {Troels Wesenberg} and Olsen, {Niels Vidiendal} and Christian Krarup",
note = "{\textcopyright} 2014 The Authors. The Journal of Physiology {\textcopyright} 2014 The Physiological Society.",
year = "2014",
month = jul,
day = "1",
doi = "10.1113/jphysiol.2014.270827",
language = "English",
volume = "592",
pages = "2735--50",
journal = "The Journal of physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "13",

}

RIS

TY - JOUR

T1 - Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans

AU - Moldovan, Mihai

AU - Lange, Kai Henrik Wiborg

AU - Aachmann-Andersen, Niels Jacob

AU - Kjær, Troels Wesenberg

AU - Olsen, Niels Vidiendal

AU - Krarup, Christian

N1 - © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.

AB - The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.

U2 - 10.1113/jphysiol.2014.270827

DO - 10.1113/jphysiol.2014.270827

M3 - Journal article

C2 - 24710060

VL - 592

SP - 2735

EP - 2750

JO - The Journal of physiology

JF - The Journal of physiology

SN - 0022-3751

IS - 13

ER -

ID: 44628201