Influence of low-dose naloxone on the analgesic efficacy of morphine in rats / 解放军医学杂志

ABSTRACT

Objective To determine the optimal dose range of naloxone to enhance the analgesic effect of morphine.Methods One half of a total of 84 adult male Sprague-Dawley rats were randomly assigned into seven groups(6 rats for each group).Rats in group NS received normal saline,and in group M received 6mg/kg of morphine.Different doses of naloxone(1?g/kg,100ng/kg,10ng/kg,1ng/kg and 0.1ng/kg)with 6mg/kg of morphine were given to the rats in group MN1,group MN2,group MN3,group MN4 and group MN5.Pain thresholds were determined at different time points before and after subcutaneous injection of normal saline or morphine or mixture of the drugs(morphine and naloxone).Another 42 rats were randomly assigned into seven groups similar to the above grouping,but the morphine doses for group M and groups MN were changed to 2mg/kg.Acute pain was prodused by an in cision on the hind paw.Then they were given subcutaneous injection of the drugs in different doses as categorized above.Cumulative pain scores were observed within an hour.Results Compared with group NS,the pain thresholds of all the other groups were significantly increased at the time points from 5 minutes to 120 minutes after subcutaneous injection(P0.05).Conclusions Low-dose of naloxone can enhance the analgesic effect of morphine,and the dose range 1ng/kg~100ng/kg may be acceptable.Dose of 1?g/kg naloxone may antagonize the analgesic effect of morphine,while dose of 0.1ng/kg naloxone,perhaps,is too low to show an effect.