Low-concentration Lidocaine Rapidly Inhibits Axonal Transport in Cultured Mouse Dorsal Root Ganglion Neurons

Kanai, Akifumi; Hiruma, Hiromi; Katakura, Takashi; Sase, Sumi; Kawakami, Tadashi; Hoka, Sumio

doi:10.1097/00000542-200109000-00021

Cited by 47 publications

(31 citation statements)

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“…Lidocaine, a local anesthetic, also reportedly impairs axonal transport (19,26). We found that lidocaine decreased the number of anterograde and retrograde axonal transport of CM-DiI-labeled particles.…”

Section: Discussionmentioning

confidence: 60%

“…The minimum dose of lidocaine that affected axonal transport was 10 mM. This effective concentration is higher than that observed with DIC microscopy, in which lidocaine inhibits axonal transport with an IC 50 of 10 μM (19). Although the reasons for this discrepancy are unknown, it may be due to differences in the moving particles or membranous organelles which were visualized by the two different experimental systems.…”

Section: Discussionmentioning

confidence: 72%

“…We first tested the effects of lidocaine on axonal transport in DRG neurons. Lidocaine is widely used as a local anesthesia and has been reported to exert an inhibitory effect on axonal transport (19). Lidocaine (10 mM) decreased the number and the velocity of the CM-DiI-labeled vesicles (Fig.…”

Section: Assessment Of the Effects Of Drugs On Axonal Transport Of CMmentioning

confidence: 92%

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Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

et al. 2010

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Abstract. Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 72%

Section: Assessment Of the Effects Of Drugs On Axonal Transport Of CMmentioning

confidence: 92%

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Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

et al. 2010

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“…Although calcium is a requirement for axonal transport, increases in cytoplasmic calcium levels also inhibit mitochondrial transport (Kanai et al, 2001;Kanje et al, 1981;Kendal et al, 1983). Because mitochondria are involved in calcium regulation (Budd and Nicholls, 1996;Rizzuto, 2001), it will be important to understand how intracellular ionic composition modulates mitochondrial transport.…”

Section: Ionic Blockade Of Fast Axonal Transport?mentioning

confidence: 99%

Axonal mitochondrial transport and potential are correlated

Miller

Sheetz

2004

Journal of Cell Science

459

387

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Disruption of axonal transport leads to a disorganized distribution of mitochondria and other organelles and is thought to be responsible for some types of neuronal disease. The reason for bidirectional transport of mitochondria is unknown. We have developed and applied a set of statistical methods and found that axonal mitochondria are uniformly distributed. Analysis of fast axonal transport showed that the uniform distribution arose from the clustering of the stopping events of fast axonal transport in the middle of the gaps between stationary mitochondria. To test whether transport was correlated with ATP production, we added metabolic inhibitors locally by micropipette. Whereas applying CCCP (a mitochondrial uncoupler) blocked mitochondrial transport, as has been previously reported, treatment with antimycin (an inhibitor of electron transport at complex III) caused increases in retrograde mitochondrial transport. Application of 2-deoxyglucose did not decrease transport compared with the mannitol control. To determine whether mitochondrial transport was correlated with mitochondrial potential, we stained the neurons with the mitochondrial potential-sensing dye JC-1. We found that ∼90% of mitochondria with high potential were transported towards the growth cone and ∼80% of mitochondria with low potential were transported towards the cell body. These experiments show for the first time that a uniform mitochondrial distribution is generated by local regulation of the stopping events of fast mitochondrial transport, and that the direction of mitochondrial transport is correlated with mitochondrial potential. These results have implications for axonal clogging, autophagy, apoptosis and Alzheimer's disease.

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“…19, 20 , 21 Mitochondrial damage as a contributing factor is suggested by loss of mitochondrial potential22 and leakage of cytochrome C, 20,22 but this is not a consistent finding. 21,23 Other studies focus on direct neuronal membrane damage by local anesthetics, 19,24,25 and inhibition of axonal transport has likewise been implicated, 26,27 probably through loss of axonal microtubules. 28 There is also evidence of damage from the generation of oxygen free radicals.…”

Section: Toxicity Of Injected Solutionmentioning

confidence: 99%

Pathophysiology of Peripheral Nerve Injury During Regional Anesthesia

Hogan¹

2008

Regional Anesthesia and Pain Medicine

129

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Low-concentration Lidocaine Rapidly Inhibits Axonal Transport in Cultured Mouse Dorsal Root Ganglion Neurons

Abstract: Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II.

Cited by 47 publications

References 0 publications

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

Axonal mitochondrial transport and potential are correlated

Pathophysiology of Peripheral Nerve Injury During Regional Anesthesia

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