An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability
Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to...
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doaj-e4520bc70f5546dabe3184dc0025244d2020-11-24T20:43:09ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-07-011210.3389/fnins.2018.00494387577An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and ExcitabilityMihai Moldovan0Mihai Moldovan1Susana Alvarez2Christian Rothe3Thomas L. Andresen4Andrew Urquhart5Kai H. W. Lange6Christian Krarup7Christian Krarup8Department of Neuroscience, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Neurophysiology, Rigshospitalet, Copenhagen, DenmarkDepartment of Neuroscience, University of Copenhagen, Copenhagen, DenmarkDepartment of Anesthesia, Nordsjællands Hospital, Hillerød, DenmarkDepartment for Micro- and Nanotechnology, Technical University of Denmark, Lyngby, DenmarkDepartment for Micro- and Nanotechnology, Technical University of Denmark, Lyngby, DenmarkDepartment of Anesthesia, Nordsjællands Hospital, Hillerød, DenmarkDepartment of Neuroscience, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Neurophysiology, Rigshospitalet, Copenhagen, DenmarkPeripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model.https://www.frontiersin.org/article/10.3389/fnins.2018.00494/fullliposomesperipheral nerve blockthreshold-trackingin vivo imaginglidocaine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mihai Moldovan Mihai Moldovan Susana Alvarez Christian Rothe Thomas L. Andresen Andrew Urquhart Kai H. W. Lange Christian Krarup Christian Krarup |
spellingShingle |
Mihai Moldovan Mihai Moldovan Susana Alvarez Christian Rothe Thomas L. Andresen Andrew Urquhart Kai H. W. Lange Christian Krarup Christian Krarup An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability Frontiers in Neuroscience liposomes peripheral nerve block threshold-tracking in vivo imaging lidocaine |
author_facet |
Mihai Moldovan Mihai Moldovan Susana Alvarez Christian Rothe Thomas L. Andresen Andrew Urquhart Kai H. W. Lange Christian Krarup Christian Krarup |
author_sort |
Mihai Moldovan |
title |
An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability |
title_short |
An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability |
title_full |
An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability |
title_fullStr |
An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability |
title_full_unstemmed |
An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability |
title_sort |
in vivo mouse model to investigate the effect of local anesthetic nanomedicines on axonal conduction and excitability |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-07-01 |
description |
Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model. |
topic |
liposomes peripheral nerve block threshold-tracking in vivo imaging lidocaine |
url |
https://www.frontiersin.org/article/10.3389/fnins.2018.00494/full |
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