Beloeil Hélène, Ababneh Zaid, Chung Richard, Zurakowski David, Mulkern Robert V, Berde Charles B
Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Anesthesiology. 2006 Jul;105(1):128-38. doi: 10.1097/00000542-200607000-00022.
Local anesthetics exert antiinflammatory actions. To elucidate potential mechanisms, the authors examined effects of bupivacaine or tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema, and stimulated cytokine production in circulating blood cells.
Twelve groups of rats (n = 9-12) received injections in three sites: (1) right or left hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically (subcutaneously in the upper back). Sciatic and systemic injections were performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and motor block were assessed behaviorally, and paw edema was quantified by magnetic resonance imaging. Stimulated production of tumor necrosis factor alpha, interleukin 10, and interleukin 1beta in whole blood cultures was measured by enzyme-linked immunosorbent assay.
Either ipsilateral or contralateral sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan-induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in suppressing systemic tumor necrosis factor alpha and interleukin 1beta by all three routes, whereas tetrodotoxin was ineffective by all three routes.
Bupivacaine and tetrodotoxin, via a contralateral or ipsilateral sciatic block, attenuate local inflammatory edema and hyperalgesia induced by hind paw injection of carrageenan in rats. Mechanisms underlying contralateral effects of sciatic blockade remain unexplained. Bupivacaine inhibits carrageenan-evoked systemic cytokine production by a mechanism not shared by tetrodotoxin; this action may involve tetrodotoxin-resistant sodium channels or a variety of non-sodium-channel targets.
局部麻醉药具有抗炎作用。为阐明其潜在机制，作者研究了通过同侧或对侧坐骨神经阻滞或全身给药给予大鼠布比卡因或河豚毒素，对角叉菜胶诱导的后爪痛觉过敏、水肿以及循环血细胞中细胞因子产生的影响。
12组大鼠（每组9 - 12只）在三个部位接受注射：（1）右后爪或左后爪（注射角叉菜胶或生理盐水），（2）左坐骨神经阻滞，（3）全身给药（背部皮下）。坐骨神经和全身注射使用肾上腺素加布比卡因、河豚毒素或生理盐水；6小时后重复注射。15小时后，通过行为学评估痛觉过敏和/或感觉及运动阻滞情况，并通过磁共振成像对角爪水肿进行定量分析。采用酶联免疫吸附测定法测量全血培养物中肿瘤坏死因子α、白细胞介素10和白细胞介素1β的刺激产生量。
使用布比卡因或河豚毒素进行同侧或对侧坐骨神经阻滞均可减轻角叉菜胶诱导的水肿和痛觉过敏。全身给予布比卡因和河豚毒素对预防水肿和痛觉过敏无效。布比卡因通过所有三种途径均能有效抑制全身肿瘤坏死因子α和白细胞介素1β，而河豚毒素通过所有三种途径均无效。
布比卡因和河豚毒素通过对侧或同侧坐骨神经阻滞，可减轻大鼠后爪注射角叉菜胶诱导的局部炎症性水肿和痛觉过敏。坐骨神经阻滞对侧效应的潜在机制尚不清楚。布比卡因通过一种河豚毒素不具备的机制抑制角叉菜胶诱发的全身细胞因子产生；这种作用可能涉及对河豚毒素耐药的钠通道或多种非钠通道靶点。
