Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.
Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.
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DOI：
10.1097/aln.0b013e3182a2a561
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发表时间：
2014-01
期刊：
影响因子：
8.8
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Doan LV;Eydlin O;Piskoun B;Kline RP;Recio-Pinto E;Rosenberg AD;Blanck TJ;Xu F
神经轴局部麻醉剂可能具有神经系统并发症，被认为是由于神经毒性。局部麻醉剂的主要作用部位是背根神经节（DRG）神经元。生理差异已注意到年轻和成年DRG神经元之间，因此，我们研究是否有差异，在新生儿和成年大鼠DRG神经元中的钙和利多卡因毒性的利多卡因诱导的变化。培养出生后7天（P7）和成年大鼠的DRG神经元。用钙指示剂Fluo-4检查利多卡因诱导的细胞溶质钙变化。将细胞与不同浓度的利多卡因一起孵育，并使用钙黄绿素AM和乙锭同型二聚体-1染色检查活力。在与利多卡因孵育后进行半胱天冬酶-3/7活化的实时成像。在P7神经元中KCl诱导的平均钙瞬变更大（p < 0.05），并且利多卡因在两个年龄段中显著抑制KCl诱导的钙反应（p < 0.05）。KCl诱发的钙增加的频率分布直方图在P7比成人神经元更不均匀。使用利多卡因，KCl诱导的钙瞬变在两个年龄段变得更加均匀，但组间仍有差异。有趣的是，在两个年龄段中，利多卡因以剂量依赖性方式降低细胞活力。利多卡因治疗也以剂量和时间依赖性方式激活caspase-3/7。尽管P7和成人DRG神经元存在生理差异，但利多卡因的细胞毒性在体外P7和成人DRG神经元中相似。利多卡因和氯化钾诱发的钙反应的差异表明，利多卡因细胞毒性的相似性涉及其他行动，除了利多卡因诱发的影响胞浆钙反应。
Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action for local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, we examined whether there were differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. The mean KCl-induced calcium transient was greater in P7 neurons (p < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (p < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.