Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Geriatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Anesthesiology. 2023 Dec 1;139(6):782-800. doi: 10.1097/ALN.0000000000004761.
Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. This study investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling.
A sciatic nerve transection-repair (SNT) model was established in adult Sprague-Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 μM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiologic, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and Western blotting.
Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory-motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiologic (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P < 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of neurofilament 200 [NF-200]-positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P < 0.001). The authors also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9 days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P < 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467.
Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling.
罗哌卡因持续神经阻滞常用于创伤性周围神经损伤修复手术后。在外周神经损伤后，河豚毒素抗性电压门控钠通道 Nav1.8 上调，并有助于巨噬细胞炎症。本研究探讨了罗哌卡因是否通过 Nav1.8 介导的巨噬细胞信号转导促进周围神经再生。
在成年雄性和雌性 Sprague-Dawley 大鼠中建立坐骨神经横断修复（SNT）模型。大鼠在损伤部位或骶骨附近接受 0.2%罗哌卡因或 10 μM Nav1.8 选择性抑制剂 A-803467 治疗 3 天。通过行为、电生理和形态学检查评估神经再生。此外，通过免疫染色、酶联免疫吸附试验和 Western blot 评估髓鞘碎片清除、巨噬细胞表型、Nav1.8 表达和神经肽表达。
与 SNT 加载体组相比，两组罗哌卡因组的感觉、运动和感觉运动协调功能均显著改善。电生理（均值±标准差：振幅恢复指数，载体 0.43±0.17 比罗哌卡因 0.83±0.25，n=11，P<0.001）和组织学分析共同表明，罗哌卡因显著促进轴突再生（神经丝 200 [NF-200]阳性面积的百分比：载体 19.88±2.81 比罗哌卡因 31.07±2.62，n=6，P<0.001）。作者还发现，与 SNT 加载体组相比，SNT 加罗哌卡因组髓鞘碎片清除更快，巨噬细胞浸润明显增加，从 M1 向 M2 表型转变。此外，罗哌卡因显著抑制坐骨神经横断后 9 天 Nav1.8 的上调（载体 4.12±0.30 倍比罗哌卡因 2.75±0.36 倍，n=5，P<0.001），同时趋化因子配体 2 和 P 物质的表达增加。当使用选择性 Nav1.8 通道抑制剂 A-803467 时，也观察到类似的变化。
罗哌卡因持续神经阻滞促进受损坐骨神经的结构和功能恢复，可能通过调节 Nav1.8 介导的巨噬细胞信号转导。
