Nitrendipine blocks the nociceptive effects of chronically administered ethanol.
Nitrendipine blocks the nociceptive effects of chronically administered ethanol.
复制标题
尼群地平可阻断长期服用乙醇的伤害性作用。
DOI：
10.1097/01.alc.0000024127.01977.50
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Gatch,MichaelB
中科院分区：
文献类型：
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作者：
Gatch,MichaelB
背景：钙通道阻滞剂可防止对乙醇产生耐受性，防止癫痫发作和其他乙醇戒断症状。钙通道也可能介导对乙醇抗伤感受作用的耐受性的发展。方法采用辐射热甩尾法评价尼群地平（一种二氢吡啶L型钙通道阻滞剂）对乙醇诱导大鼠伤害感受变化的影响。在四组大鼠中测试了乙醇的慢性影响，这些大鼠接受了10天的液体饮食。各组每天两次注射生理盐水或尼群地平（1、5或10 mg/kg）。甩尾潜伏期分别在第0天（基线）、第2天、第4天、第6天、第8天和第10天以及在移除流食后12小时进行测量。结果慢性乙醇暴露在暴露第4天产生最大水平的抗伤性。观察到的抗痛觉水平在第8天逐渐下降到基线水平。在乙醇戒断期间，观察到甩尾潜伏期明显降低，低于基线（痛觉过敏）。反复给药尼群地平阻断慢性乙醇的抗痛觉作用，防止乙醇戒断引起的痛觉过敏。最高剂量的尼群地平（10 mg/kg，每日两次）减少了乙醇饮食的消耗。结论l‐型钙通道阻滞剂可阻断乙醇戒断期间的痛觉过敏，并可能介导（至少部分）慢性乙醇的抗伤感受作用。
BackgroundCalcium channel blockers prevent the development of tolerance to ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium channels may also mediate the development of tolerance to the antinociceptive effects of ethanol.MethodsA radiant‐heat tail‐flick assay was used to assess the effects of nitrendipine, a dihydropyridine L‐type calcium channel blocker, on ethanol‐induced changes in nociception in rats. Chronic effects of ethanol were tested in four groups of rats, which received 10 days of exposure to a liquid diet. The groups received twice‐daily injections of saline or nitrendipine (1, 5, or 10 mg/kg). Tail‐flick latencies were measured on days 0 (baseline), 2, 4, 6, 8, and 10 and at 12 hr after removal of the liquid diet.ResultsChronic exposure to ethanol produced maximal levels of antinociception by day 4 of exposure. The observed level of antinociception gradually decreased to baseline levels by day 8. Marked decreases in tail‐flick latencies below baseline (hyperalgesia) were observed during ethanol withdrawal. Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet.ConclusionsL‐type calcium channel blockers block hyperalgesia during ethanol withdrawal and may mediate, at least in part, the antinociceptive effects of chronic ethanol.