A sciatic nerve blockade method to differentiate drug-induced local anesthesia from neuromuscular blockade in mice

Leszczynska, Krystyna; Kau, Sen T.

doi:10.1016/1056-8719(92)90026-w

Cited by 49 publications

(34 citation statements)

References 16 publications

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“…LA activity was assessed by the loss of motor control in the injected limb with the scores: 0 (normal movement); 1 (unable to flex the limb completely); and 2 (total paralysis). 10 Any animal that could not use the injected limb to walk normally on the top and on the inverted wire mesh screen was considered to have a positive response to local anesthesia. The efficacy of motor blockade was evaluated every minute, from one to five minutes, and thereafter every ten minutes up to one hour following the injection.…”

mentioning

confidence: 99%

“…1 Sciatic nerve blockade was used as an experimental model, providing information about the intensity and duration of blockade induced by LA agents. 10 Many studies have utilized motor or sensory blockade to assess LA activity in rats [14][15][16][17] and mice. [18][19][20] Our experimental model was shown to be appropriate to monitor the duration of motor and sensory blockade induced by LA in mice.…”

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confidence: 99%

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Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

et al. 2004

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P Pu ur rp po os se e: : Liposomal formulations of local anesthetics (LA) are able to control drug-delivery in biological systems, prolonging their anesthetic effect. This study aimed to prepare, characterize and evaluate in vivo drug-delivery systems, composed of large unilamellar liposomes (LUV), for bupivacaine (BVC) and mepivacaine (MVC).M Me et th ho od ds s: : BVC and MVC hydrochloride were encapsulated into LUV (0.4 µm) composed of egg phosphatidylcholine, cholesterol and α-tocopherol (4:3:0.07 molar ratio) to final concentrations of 0.125, 0.25, 0.5% for BVC and 0.5, 1, 2% for MVC. Motor function and antinociceptive effects were evaluated by sciatic nerve blockade induced by liposomal and plain formulations in mice.R Re es su ul lt ts s: : Liposomal formulations modified neither the intensity nor the duration of motor blockade compared to plain solutions. Concerning sensory blockade, liposomal BVC (BVC LUV ) showed no advantage relatively to the plain BVC injection while liposomal MVC (MVC LUV ) improved both the intensity (1.4-1.6 times) and the duration of sensory blockade (1.3-1.7 times) in comparison to its plain solution (P < 0.001) suggesting an increased lipid solubility, availability and controlled-release of the drug at the site of injection.C Co on nc cl lu us si io on n: : MVC LUV provided a LA effect comparable to that of BVC. We propose MVC LUV drug delivery as a potentially new therapeutic option for the treatment of acute pain since the formulation enhances the duration of sensory blockade at lower concentrations than those of plain MVC. de 0,125, 0,25, 0,5 % pour la BVC et 0,5 Objectif : Des préparations liposomales d'anesthésiques locaux (AL) peuvent contrôler l'administration de médicaments dans les systèmes biologiques, prolongeant leur effet anesthésique. Notre objectif était de préparer, caractériser et évaluer des systèmes d'administration de médicaments in vivo, composés de gros liposomes unilamellaires (GLU), pour la bupivacaïne (BVC) et la mépivacaïne (MVC). Méthode : Le chlorhydrate de BVC et de MVC a été mis en capsules dans des GLU (0,4 µm) composés de lécithine d'oeuf, de cholestérol et de α-tocophérol (concentration molaire 4:3:0,07) pour obtenir des concentrations finales

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Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

et al. 2004

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“…Seizure induction by propranolol in humans is rare cases, and propranolol is also known for its antiepileptic activity in experimental animals (Khanna et al, 1989). In addition, propranolol is reported as possessing β-blocking and local anesthetic activity (Leszczynska and Kau, 1992). From the above, zebrafish might have developed a tolerance for seizures caused by propranolol.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish

et al. 2014

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-As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery.Key words: Zebrafish, Locomotor activity, Seizure, Extending exposure time, Flashlight stimulation Correspondence: Naoteru Koseki (E-mail: naoteru-koseki@ds-pharma.co.jp) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.39, No.4, 579-600, 2014 Vol. 39 No. 4 579 through the blood-brain barrier (BBB). Since such assays are conducted with a focus on specific neural networks or cells associated with seizures, performing an evaluation using above alternative methods is direct and limited. On the basis of the aforementioned findings, a test system that can take pharmacokinetic effects into account and can be used to perform an evaluation under conditions closer to whole body is considered desirable. As such, an in vivo evaluation system using Caenorhabditis elegans (C. elegans), which is one of the nematodes with gamma-aminobutyratergic (GABAergic) neurons related to seizures, has been reported (Locke et al., 2006;Pandey et al., 2010), and an evaluation using behavioral assessment of such organism is expected. However, nematodes are very different from mammals in terms of the anatomical structure of central nervous system (CNS) or pharmacokinetics. Therefore, performing an assessment which approximates the evaluation of a conventional study using rodents is considered to be difficult.Zebrafish is a vertebrate and its genomic homology to humans is approximately 70% (Howe et al., 2013). In addition, zebrafish can be utilized in early stage drug screening in recent decades. For these reasons, an evaluation using zebrafish has recently been given attention as a novel in vivo evaluation system for safety assessment. Since zebrafish have tele...

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“…who is an experienced nurse anesthetist familiar with nerve block procedures. He followed the method developed by Leszczynska and Kau [12]. Briefly, each mouse was placed in a cotton gauze padded plastic tube (4.5 in high, 1.2 in diameter) head down, and the right hind limb was grasped at the knee by padded forceps.…”

Section: Injection Proceduresmentioning

confidence: 99%

“…All mice were assessed for limb weakness throughout the study using an inverted walking test following the procedure of Leszczynska and Kau [12]. The mouse was placed on a 15 !…”

Section: Inverted Walking Test For Limb Weaknessmentioning

confidence: 99%

Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

Smith

Lindsay

2003

Pharmacology

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Sodium channel drugs were used to modulate the anesthetic effects of bupivacaine in mice. Anesthesia was measured following perisciatic injection of bupivacaine with vehicle or neurotoxin in the popliteal region. The site 1 Na⁺ channel blocker tetrodotoxin alone was inactive, but increased the anesthetic effects of bupivacaine. We hypothesized that the site 2 and site 3 Na⁺ channel openers veratridine and anemone toxin II (ATXII), respectively, would antagonize bupivacaine. Paradoxically, both drugs enhanced bupivacaine. In bupivacaine-treated mice, a significant correlation was observed between limb weakness scores and paw withdrawal latencies. The correlation coefficients were higher when tetrodotoxin, veratridine, or ATXII was coadministered with bupivacaine. In conclusion, veratridine and ATXII may have increased the stimulus-dependent binding of bupivacaine to Na⁺ channels, thereby increasing the anesthetic effects of bupivacaine.

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A sciatic nerve blockade method to differentiate drug-induced local anesthesia from neuromuscular blockade in mice

Cited by 49 publications

References 16 publications

Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish

Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

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