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镇痛增强及吗啡耐受性预防:ω-3脂肪酸联合治疗的有益作用

Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids.

作者信息

Escudero Graciela E, Romañuk Carolina B, Toledo María E, Olivera María E, Manzo Ruben H, Laino Carlos H

机构信息

Instituto de Biotecnología, Centro de Investigación e Innovación Tecnológica - CENIIT, Universidad Nacional de La Rioja, La Rioja, Argentina.

Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.

出版信息

J Pharm Pharmacol. 2015 Sep;67(9):1251-62. doi: 10.1111/jphp.12416. Epub 2015 May 25.

Abstract

OBJECTIVES

Recent evidence associates omega-3 fatty acids (O3) with pain reduction. The aim of this work was to evaluate the antinociceptive effect of O3, either alone or in combination with morphine after acute and chronic administration in rats. As well, a new pharmaceutical mixture that allows the concomitant administration of O3 and morphine as an oral solution was developed.

METHODS

Animals were fed on a control or an experimental diet supplemented with O3. They were subjected to the hot-plate test to assess analgesic effect and tolerance to the analgesic effect of morphine. The open-field test was carried out to determine if the differences in the response latency can be related to non-specific sedative effects.

KEY FINDINGS

O3 dietary supplementation increased the response latency compared with the control group. Acute treatment with morphine in these groups resulted in an additive antinociceptive effect not related to locomotor activity. Chronic coadministration of morphine with O3 attenuated the development of tolerance. Oral administration of the new pharmaceutical mixture showed analgesic activity with a subtherapeutic dose of morphine.

CONCLUSION

This finding suggests a role for O3 as adjuncts to opioids in pain therapy and might contribute to the reduction of the occurrence of morphine side-effects.

摘要

目的

近期证据表明ω-3脂肪酸(O3)与疼痛减轻有关。本研究的目的是评估O3单独或与吗啡联合使用在大鼠急性和慢性给药后的镇痛作用。此外,还研发了一种新的药物混合物,可将O3和吗啡制成口服溶液同时给药。

方法

给动物喂食对照饮食或补充了O3的实验饮食。对它们进行热板试验以评估镇痛效果以及对吗啡镇痛作用的耐受性。进行旷场试验以确定反应潜伏期的差异是否与非特异性镇静作用有关。

主要发现

与对照组相比,补充O3的饮食增加了反应潜伏期。这些组中吗啡的急性治疗产生了与运动活动无关的相加镇痛作用。吗啡与O3的慢性联合给药减弱了耐受性的发展。口服新的药物混合物在亚治疗剂量的吗啡时显示出镇痛活性。

结论

这一发现表明O3在疼痛治疗中作为阿片类药物的辅助剂具有一定作用,可能有助于减少吗啡副作用的发生。

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