钙通道阻滞剂在脊髓水平增强吗啡的镇痛作用。

Potentiation of antinociceptive effects of morphine by calcium-channel blockers at the level of the spinal cord.

作者信息

Omote K, Sonoda H, Kawamata M, Iwasaki H, Namiki A

机构信息

Department of Anesthesiology, Sapporo Medical College and Hospital, Japan.

出版信息

Anesthesiology. 1993 Oct;79(4):746-52. doi: 10.1097/00000542-199310000-00017.

DOI:10.1097/00000542-199310000-00017

PMID:8214754

Abstract

BACKGROUND

Opioids inhibit voltage-dependent calcium-channel conductance, which is essential for the nervous system to be able to signal a painful event. Accordingly, interference with calcium-channel conductance may enhance opioid analgesia. The current study was designed to investigate the effects of calcium-channel blocking drugs on the antinociception of morphine at the level of the spinal cord.

METHODS

Rats were chronically implanted with catheters in the lumbar intrathecal space. Tail-flick test was used to assess thermal nociception. Intrathecally administered drugs were morphine, calcium-channel blockers (verapamil, diltiazem, and nicardipine), or a combination of morphine and calcium-channel blocker.

RESULTS

Intrathecal administration of morphine produced a significant dose-dependent antinociception in the tail-flick test. In contrast, intrathecal administration of calcium-channel blockers, verapamil, diltiazem, and nicardipine, did not show any antinociception at the employed doses. However, when intrathecally administered calcium-channel blockers, verapamil (50 micrograms), diltiazem (100 micrograms), or nicardipine (20 micrograms), were combined with ineffective (0.25, 0.5, 1, or 2 micrograms) or moderately effective (5 micrograms) doses of intrathecally administered morphine, significant antinociception was produced. These interactions were synergistic. There were no significant changes in MAP or HR after the intrathecal administration of 200 micrograms verapamil or 2 micrograms morphine combined with 50 micrograms verapamil.

CONCLUSIONS

The authors interpreted these results to indicate that calcium-channel blocking drugs synergistically potentiate the analgesic effects of morphine at the level of the spinal cord. Before these results can be translated into clinical use, however, adequate toxicity studies must be conducted to examine the effect of the perispinal administration of calcium-channel blocking drugs on spinal cord function.

摘要

背景

阿片类药物可抑制电压依赖性钙通道电导，而该电导对于神经系统发出疼痛信号至关重要。因此，干扰钙通道电导可能增强阿片类药物的镇痛作用。本研究旨在探讨钙通道阻滞剂对脊髓水平吗啡镇痛作用的影响。

方法

大鼠在腰段鞘内间隙长期植入导管。采用甩尾试验评估热痛觉。鞘内注射的药物为吗啡、钙通道阻滞剂（维拉帕米、地尔硫䓬和尼卡地平），或吗啡与钙通道阻滞剂的组合。

结果

鞘内注射吗啡在甩尾试验中产生了显著的剂量依赖性镇痛作用。相比之下，鞘内注射钙通道阻滞剂维拉帕米、地尔硫䓬和尼卡地平在所使用的剂量下未显示出任何镇痛作用。然而，当鞘内注射钙通道阻滞剂维拉帕米（50微克）、地尔硫䓬（100微克）或尼卡地平（20微克）与无效剂量（0.25、0.5、1或2微克）或中等有效剂量（5微克）的鞘内注射吗啡联合使用时，产生了显著的镇痛作用。这些相互作用是协同的。鞘内注射200微克维拉帕米或2微克吗啡与50微克维拉帕米联合使用后，平均动脉压（MAP）或心率（HR）无显著变化。