Use of bulleyaconitine A as an adjuvant for prolonged cutaneous analgesia in the rat.
Use of bulleyaconitine A as an adjuvant for prolonged cutaneous analgesia in the rat.
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使用Bulleyaconitine A作为大鼠长时间皮肤镇痛的佐剂。
DOI：
10.1213/ane.0b013e318182401b
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发表时间：
2008-10
影响因子：
5.7
通讯作者：
Wang GK
中科院分区：
文献类型：
--
作者：
Wang CF;Gerner P;Schmidt B;Xu ZZ;Nau C;Wang SY;Ji RR;Wang GK
草乌甲素（Bulleyaconitine A，BLA）是从豆科植物中分离得到的一种镇痛、抗炎药物。BLA有几个潜在的靶点，包括电压门控Na+通道。我们测试是否BLA引起持久的皮肤镇痛，当共注射利多卡因和肾上腺素，作为一个模型，延长浸润麻醉。通过膜片钳技术在表达Nav1.7和Nav1.8神经元Na+通道的HEK 293 t细胞中评估BLA的局部麻醉特性，这两种通道对伤害性感受至关重要。通过大鼠剃毛的背部皮肤皮下注射药物溶液（0.6 mL）。通过针刺评价皮肤干肌反射的抑制。皮肤横截面用苏木精和伊红或用抗PGP9.5的抗体染色。当偶尔刺激至+50 mV持续3 ms时，10 µM BLA与静息或失活Nav1.7和Nav1.8 Na+通道的相互作用最小。然而，当以2 Hz刺激1000个脉冲时，BLA使其峰值Na+电流降低>90%。这种使用依赖性抑制在15分钟洗涤后没有显著逆转。注射利多卡因（0.5%）/肾上腺素（1：200，000）后，大鼠的完全伤害性阻滞持续约1 h;约6 h后完全恢复。将0.125 mM BLA与利多卡因/肾上腺素共同注射可将完全伤害性阻滞的持续时间延长至24 h。大约6天后完全恢复。皮肤组织学包括外周神经纤维似乎不受BLA的影响。BLA以使用依赖性方式抑制Nav1.7和Nav1.8 Na+电流。联合注射≤0.125 mM的BLA与利多卡因和肾上腺素可使皮肤完全镇痛，持续长达24小时，无不良反应。
Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na+ channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na+ channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. BLA at 10 µM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na+ channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na+ currents were >90% reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. BLA inhibits Nav1.7 and Nav1.8 Na+ currents in a use-dependent manner. Co-injection of BLA at ≤0.125 mM with lidocaine and epinephrine elicits complete cutaneous analgesia that lasts for up to 24 h without adverse effects.
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