Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Departments of Otolaryngology and Neuroscience, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Mar Drugs. 2011 Dec;9(12):2717-2728. doi: 10.3390/md9122717. Epub 2011 Dec 15.
Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.
目前市售的局部麻醉药在人体中的镇痛作用持续时间一般小于 12 小时。长效局部麻醉药将有助于术后镇痛。先前的研究表明，在大鼠中，河豚毒素（TTX）与布比卡因联合使用对坐骨神经阻滞持续时间有超相加作用。在这些研究中，肾上腺素与 TTX 联合使用可使阻滞时间延长 10 倍以上，同时降低全身毒性。TTX 作为 Tectin 制剂，正在进行 III 期临床试验，作为一种用于治疗慢性癌痛的可注射系统镇痛剂。在这里，我们研究了 Tectin 与 0.25%布比卡因（2.5mg/ml）溶液联合应用于局部神经阻滞时的剂量-持续时间关系和坐骨神经组织学，无论是否含有肾上腺素 5µg/ml（1:200,000）。在 Sprague-Dawley 大鼠中进行经皮坐骨神经阻滞，并使用不同的 Tectin-布比卡因-肾上腺素组合对感觉阻滞的强度和持续时间进行盲法测试。采用方差分析和事后 Sidak 检验对组间比较进行分析。对神经进行盲法检查，以确定是否有损伤迹象。与布比卡因 0.25%（无 Tectin 和肾上腺素）相比，含有 Tectin 10µM 和肾上腺素 5µg/ml 的布比卡因 0.25%阻滞时间延长约 3 倍（P<0.001），与含有肾上腺素 5µg/ml 的布比卡因 0.25%阻滞时间延长约 3 倍（P<0.001）。所有组的神经组织学均为良性。布比卡因 0.25%中加入 Tectin 和肾上腺素 5µg/ml 的组合似乎有希望延长局部麻醉的持续时间。
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