![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 285, Issue 2, 413-421, May 1998
Departments of Anesthesiology, Anatomy, Medicine, and Oral Surgery
and Division of Neuroscience, University of California, San
Francisco, California
Evidence from both clinical studies and animal models suggests that the
local anesthetic, lidocaine, is neurotoxic. However, the mechanism of
lidocaine-induced toxicity is unknown. To test the hypothesis that
toxicity results from a direct action of lidocaine on sensory neurons
we performed in vitro histological, electrophysiological and fluorometrical experiments on isolated dorsal root ganglion (DRG)
neurons from the adult rat. We observed lidocaine-induced neuronal
death after a 4-min exposure of DRG neurons to lidocaine concentrations
as low as 30 mM. Consistent with an excitotoxic mechanism of
neurotoxicity, lidocaine depolarized DRG neurons at concentrations that
induced cell death (EC50 = 14 mM). This depolarization
occurred even though voltage-gated sodium currents and action
potentials were blocked effectively at much lower concentrations. (EC50 values for lidocaine-induced block of
tetrodotoxin-sensitive and -resistant voltage-gated sodium currents
were 41 and 101 µM, respectively.) At concentrations similar to those
that induced neurotoxicity and depolarization, lidocaine also induced
an increase in the concentration of intracellular Ca++ ions
([Ca++]i; EC50 = 21 mM)
via Ca++ influx through the plasma membrane
as well as release of Ca++ from intracellular stores.
Finally, lidocaine-induced neurotoxicity was attenuated significantly
when lidocaine was applied in the presence of nominally
Ca++-free bath solution to DRG neurons preloaded with
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our
results indicate: 1) that lidocaine is neurotoxic to sensory neurons;
2) that toxicity results from a direct action on sensory neurons; and
3) that a lidocaine-induced increase in intracellular Ca++
is a mechanism of lidocaine-induced neuronal toxicity.
This article has been cited by other articles:
|
|
 |
|
  R. Perez-Castro, S. Patel, Z. V. Garavito-Aguilar, A. Rosenberg, E. Recio-Pinto, J. Zhang, T. J. J. Blanck, and F. Xu Cytotoxicity of Local Anesthetics in Human Neuronal Cells Anesth. Analg., March 1, 2009; 108(3): 997 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Umbrain, L. Shi, M.-H. Lauwers, I. Smolders, Y. Michotte, and F. Camu Intrathecal lidocaine elevates prostaglandin E2 levels in cerebrospinal fluid: a microdialysis study in freely moving rats Br. J. Anaesth., November 1, 2008; 101(5): 716 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hiruma, K. Shimizu, T. Takenami, H. Sugie, and T. Kawakami Effects of clonidine on lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones Br. J. Anaesth., November 1, 2008; 101(5): 659 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Onizuka, T. Kasaba, and M. Takasaki The Effect of Lidocaine on Cholinergic Neurotransmission in an Identified Reconstructed Synapse Anesth. Analg., October 1, 2008; 107(4): 1236 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lirk, I. Haller, H. P. Colvin, L. Lang, B. Tomaselli, L. Klimaschewski, and P. Gerner In Vitro, Inhibition of Mitogen-Activated Protein Kinase Pathways Protects Against Bupivacaine- and Ropivacaine-Induced Neurotoxicity Anesth. Analg., May 1, 2008; 106(5): 1456 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lirk, I. Haller, H. P. Colvin, S. Frauscher, L. Kirchmair, P. Gerner, and L. Klimaschewski In Vitro, Lidocaine-Induced Axonal Injury Is Prevented by Peripheral Inhibition of the p38 Mitogen-Activated Protein Kinase, but Not by Inhibiting Caspase Activity Anesth. Analg., December 1, 2007; 105(6): 1657 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Karpie and C. R. Chu Lidocaine Exhibits Dose- and Time-Dependent Cytotoxic Effects on Bovine Articular Chondrocytes In Vitro Am. J. Sports Med., October 1, 2007; 35(10): 1621 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dogrul, S. E. Gulmez, M. S. Deveci, H. Gul, M. H. Ossipov, F. Porreca, and F. C. Tulunay The Local Antinociceptive Actions of Nonsteroidal Antiinflammatory Drugs in the Mouse Radiant Heat Tail-Flick Test Anesth. Analg., April 1, 2007; 104(4): 927 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Du, M. Yu, N. D. Volkow, A. P. Koretsky, J. S. Fowler, and H. Benveniste Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects. J. Neurosci., November 8, 2006; 26(45): 11522 - 11531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Muguruma, S. Sakura, and Y. Saito Epidural Lidocaine Induces Dose-Dependent Neurologic Injury in Rats Anesth. Analg., October 1, 2006; 103(4): 876 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sakaguchi, Y. Kuroda, and M. Hirose The antiproliferative effect of lidocaine on human tongue cancer cells with inhibition of the activity of epidermal growth factor receptor. Anesth. Analg., April 1, 2006; 102(4): 1103 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Koizumi, M. Matsumoto, A. Yamashita, S. Tsuruta, T. Ohtake, and T. Sakabe The effects of an AMPA receptor antagonist on the neurotoxicity of tetracaine intrathecally administered in rabbits. Anesth. Analg., March 1, 2006; 102(3): 930 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. A. Kolesnikov, M. Cristea, and G. W. Pasternak Analgesic Synergy Between Topical Morphine and Butamben in Mice Anesth. Analg., October 1, 2003; 97(4): 1103 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. M. Radwan, S. Saito, and F. Goto Neurotrophic Factors Can Partially Reverse Morphological Changes Induced by Mepivacaine and Bupivacaine in Developing Sensory Neurons Anesth. Analg., August 1, 2003; 97(2): 506 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamashita, M. Matsumoto, S. Matsumoto, M. Itoh, K. Kawai, and T. Sakabe A Comparison of the Neurotoxic Effects on the Spinal Cord of Tetracaine, Lidocaine, Bupivacaine, and Ropivacaine Administered Intrathecally in Rabbits Anesth. Analg., August 1, 2003; 97(2): 512 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kasaba, S. Onizuka, and M. Takasaki Procaine and Mepivacaine Have Less Toxicity In Vitro Than Other Clinically Used Local Anesthetics Anesth. Analg., July 1, 2003; 97(1): 85 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hirota, D. Smart, and D. G. Lambert The Effects of Local and Intravenous Anesthetics on Recombinant Rat VR1 Vanilloid Receptors Anesth. Analg., June 1, 2003; 96(6): 1656 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Chiang, B. Hu, J. W. Hu, J. O. Dostrovsky, and B. J. Sessle Central Sensitization of Nociceptive Neurons in Trigeminal Subnucleus Oralis Depends on Integrity of Subnucleus Caudalis J Neurophysiol, July 1, 2002; 88(1): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. M. Radwan, S. Saito, and F. Goto The Neurotoxicity of Local Anesthetics on Growing Neurons: A Comparative Study of Lidocaine, Bupivacaine, Mepivacaine, and Ropivacaine Anesth. Analg., February 1, 2002; 94(2): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Gold and P. D. Thut Lithium Increases Potency of Lidocaine-Induced Block of Voltage-Gated Na+ Currents in Rat Sensory Neurons in Vitro J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 705 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oka, M. Matsumoto, K. Ohtake, T. Kiyoshima, K. Nakakimura, and T. Sakabe The Addition of Epinephrine to Tetracaine Injected Intrathecally Sustains an Increase in Glutamate Concentrations in the Cerebrospinal Fluid and Worsens Neuronal Injury Anesth. Analg., October 1, 2001; 93(4): 1050 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Schneider and D. J. Birnbach Lidocaine Neurotoxicity in the Obstetric Patient: Is the Water Safe? Anesth. Analg., February 1, 2001; 92(2): 287 - 290. [Full Text] [PDF]
|
|
|
|
|
|
Y. A. Kolesnikov, I. Chereshnev, and G. W. Pasternak Analgesic Synergy between Topical Lidocaine and Topical Opioids J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 546 - 551. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Kanai, H. Katsuki, and M. Takasaki Lidocaine Disrupts Axonal Membrane of Rat Sciatic Nerve In Vitro Anesth. Analg., October 1, 2000; 91(4): 944 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Johnson, P. S. Hodgson, and S. S. Liu Perineural Concentration of Lidocaine Is More Relevant to Spinal Neurotoxicity than the Concentration Administered • Response Anesth. Analg., March 1, 2000; 90(3): 766 - 767. [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
