Neurotoxic effects of local anesthetics (LAs) on developing motor neurons have not been documented. We investigated the neurotoxic effects of LAs on developing motor neurons in terms of cell viability, cytotoxicity, reactive oxygen species (ROS), and apoptosis. Embryonic spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses and exposed to one of the three LAs—lidocaine, bupivacaine, or ropivacaine—at concentrations of 1, 10, 100, or 1000 µM. The exposure duration was set to 1 or 24 h. The neurotoxic effects of LAs were determined by evaluating the following: cell viability, cytotoxicity, ROS production, and apoptosis. In the 1-h exposure group, the motor neurons exposed to lidocaine and bupivacaine had reduced cell viability and increased cytotoxicity, ROS, and apoptosis in a concentration-dependent manner. Lidocaine showed the highest toxicity, followed by bupivacaine. In the 24-h exposure group, all three LAs showed significant effects (decreased cell viability and increased cytotoxicity, ROS, and apoptosis) on the motor neurons in a concentration-dependent manner. The neurotoxic effects of lidocaine were greater than those of bupivacaine and ropivacaine. Ropivacaine appeared to have the least effect on motor neurons. This study identified the neurotoxic effects of lidocaine and bupivacaine on developing spinal cord motor neurons.

Background: Emergence delirium (ED) is common in pediatric patients undergoing general anesthesia with sevoflurane. Preoperative sleep quality is associated with the risk factors for ED. However, research on the relationship between sleep quality and ED is limited. We aimed to investigate the relationship between ED and preoperative sleep quality in pediatric patients undergoing strabismus surgery.Methods: This clinical trial included pediatric patients aged 4–12 years who underwent elective strabismus surgery. The patients and their parents were questioned about the patients’ preoperative sleep quality using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For anesthesia induction, thiopental (5 mg/kg) and rocuronium (0.6 mg/kg) were used, and anesthesia was maintained with sevoflurane (minimum alveolar concentration, 1–1.5). After administration of a reversal drug, extubation was performed, and the patients were transferred to a post-anesthesia recovery unit. At 10 min after extubation, the degree of ED was measured using the pediatric anesthesia emergence delirium (PAED) and Watcha scale scores.Results: Of the 62 enrolled patients, three pediatric patients were excluded. The overall incidence of ED was 22%. A total of 59 patients were divided into the two groups. The ED group and the non-ED group comprised 13 and 46 patients. Age, height and weight were significantly lower in the ED group than in the non-ED group. Preoperative PSQI and Watcha scale score were significantly higher in the ED group than in the non-ED group. Multivariate analysis showed that age (adjusted OR [95% CI]: 0.490 [0.290–0.828],p = 0.008) and preoperative PSQI score (adjusted OR [95% CI]: 2.149[1.224–3.771],p = 0.008) was associated with ED. In sub-group analysis, PAED scale and Watcha scale scores showed a moderate correlation with preoperative sleep quality in preschool-age patients.Conclusion: In conclusion, the incidence of ED tended to be higher in younger age and poorer preoperative sleep quality in pediatric patients. In particular, the poorer sleep quality score was associated with higher incidence of ED in the preschool-age. Large-scale clinical studies and long-term follow-up studies on ED and sleep quality are required.Trial registration: This study was registered with Clinicaltrials.gov (NCT03332407) at November 5th 2017.

Jung YH, et al. J Dent Anesth Pain Med. 2022 Apr;22(2):97-105. https://doi.org/10.17245/jdapm.2022.22.2.97

Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The effect of Y-27632 and chelerythrine on the dexmedetomidine-induced intracellular calcium concentration ([Ca²⁺]_i) and tension were assessed using fura-2-loaded aortic strips. The effects of rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride on the dexmedetomidine-induced phosphorylation of CPI-17 or of the 20-kDa regulatory light chain of myosin (MLC₂₀) were investigated in rat aortic vascular smooth muscle cells. The effects of rauwolscine, Y-27632, and chelerythrine on the membrane translocation of Rho-kinase and protein kinase C (PKC) phosphorylation induced by dexmedetomidine were assessed. Y-27632 and chelerythrine each reduced the slopes of the [Ca²⁺]_i-tension curves of dexmedetomidine-induced contraction, and Y-27632 more strongly reduced these slopes than did chelerythrine. Rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride attenuated the dexmedetomidine-induced phosphorylation of CPI-17 and MLC₂₀. Taken together, these results suggest that dexmedetomidine-induced contraction involves calcium sensitization, which appears to be mediated by CPI-17 phosphorylation via Rho-kinase or PKC.

Background: The present study aimed to develop a rat model for mechanical allodynia after traumatic brain injury (TBI) and to investigate the expression of brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) using this model. Methods: A total of 180 rats were randomly allocated into three groups: a control group (group C), a sham-operated group (group S), and a controlled cortical impact induced TBI group (group T), 60 in each group. Von Frey test was performed to evaluate mechanical withdrawal thresholds. An enzyme-linked immunosorbent assay was performed to quantify BDNF level in CSF. Results: The 50% withdrawal thresholds of group T were lower than those of group C and group S at all measuring points except for the preoperative period (P = 0.026, < 0.001, and < 0.001 for POD1, POD7, and POD14, respectively). The BDNF level of group T was higher than those of group C and group S at POD1 (P = 0.005). Conclusion: Upregulation of the BDNF expression in CSF was observed in rats who developed mechanical allodynia on the day after TBI. Based on our findings, to elucidate the relationship between TBI-induced neuropathic pain and BDNF expression in CSF, further research should be carried out through a multifaceted approach to a broad spectrum of pain behavior models.

Younghoon Jung, Seungbin Park, Won Yong Lim, Jeongmin Hong, Jiseok Baik, Hyeon Jeong Lee, Jae-Young Kwon, and Eunsoo Kim. Korean J Pain -0001;0:. https://doi.org/10.3344/kjp.24419