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纳必隆对实验性热痛的镇痛和抗痛觉过敏作用。

Analgesic and antihyperalgesic effects of nabilone on experimental heat pain.

作者信息

Redmond William John, Goffaux Philippe, Potvin Stéphane, Marchand Serge

机构信息

Université de Sherbrooke, Faculté de Médecine, Sherbrooke, Québec, Canada.

出版信息

Curr Med Res Opin. 2008 Apr;24(4):1017-24. doi: 10.1185/030079908x280635. Epub 2008 Feb 22.

Abstract

OBJECTIVE

In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems.

RESEARCH DESIGN AND METHODS

A double-blind, placebo controlled, crossover study of nabilone single doses of 0.5 and 1 mg was conducted. Excitatory systems were elicited using a temporal summation test (tonic heat pain evoked by a Peltier thermode) administered before and after activation of descending inhibitory control (triggered using a counter-irritation procedure). These tests were given before and after drug treatment. Primary outcome measures included average heat pain, temporal summation of heat pain, and drug-induced changes in the strength of descending analgesia. Possible adverse reactions were monitored throughout treatment. Seven men (mean age = 22.5 years, SD = +/- 1.5) and 10 women (mean age = 23.2 years, SD = +/- 2.8) completed this study.

RESULTS

Nabilone (1 mg and 0.5 mg) did not reduce the global pain intensity experienced during tonic heat pain (all values of p > 0.18). It also failed to potentiate the strength of descending inhibitory responses (all values of p > 43). Nevertheless, at the highest dose (1 mg), and only for women, nabilone significantly (p = 0.003) dampened the temporal summation experienced during the last portion of the tonic heat pulse test (i.e., the period of time during which temporal summation is greatest). This antihyperalgesic effect was not observed for men (at either 0.5 mg or 1 mg dose), suggesting that the antihyperalgesic properties of cannabinoids are greater for women than for men. Adverse reactions encountered were generally mild and did not provoke the cessation of testing.

CONCLUSIONS

Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.

摘要

目的

在本研究中,我们探究了一种合成大麻素(纳布啡)对男性和女性实验性热痛的镇痛和抗痛觉过敏特性,以及其对下行性疼痛抑制系统的影响。

研究设计与方法

进行了一项双盲、安慰剂对照的交叉研究,给予纳布啡单次剂量0.5毫克和1毫克。在激活下行抑制控制(通过对抗刺激程序触发)之前和之后,使用时间总和测试(珀耳帖热电极诱发的持续性热痛)激发兴奋性系统。这些测试在药物治疗前后进行。主要观察指标包括平均热痛、热痛的时间总和以及药物引起的下行镇痛强度变化。在整个治疗过程中监测可能的不良反应。七名男性(平均年龄 = 22.5岁,标准差 = ±1.5)和十名女性(平均年龄 = 23.2岁,标准差 = ±2.8)完成了本研究。

结果

纳布啡(1毫克和0.5毫克)并未降低持续性热痛期间所经历的整体疼痛强度(所有p值 > 0.18)。它也未能增强下行抑制反应的强度(所有p值 > 43)。然而,在最高剂量(1毫克)时,且仅对女性而言,纳布啡显著(p = 0.003)减弱了持续性热脉冲测试最后部分所经历的时间总和(即时间总和最大的时间段)。男性(0.5毫克或1毫克剂量时)未观察到这种抗痛觉过敏效应,这表明大麻素的抗痛觉过敏特性对女性比对男性更强。所遇到的不良反应通常较轻,未导致测试停止。

结论

纳布啡未能产生镇痛作用,且未与下行性疼痛抑制系统相互作用。然而,我们发现单次1毫克剂量的纳布啡可降低女性而非男性的时间总和。尽管滴定方案和更大的受试者样本可能会产生更强的效果,但这些初步结果表明纳布啡似乎对缓解女性的痛觉过敏反应有效。进一步讨论了可能的神经生物学机制和临床意义。

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