Psychostimulant drugs potentiate morphine analgesia in the formalin test

Recent research has shown that the psychostimulant drug dextroamphetamine can increase the analgesia produced by opioids. Despite the strong, positive results in human clinical subjects and in animals, this combination is rarely used in clinical practice. The purpose of this paper is to investigate whether the psychostimulant drug methylphenidate (MP) can potentiate morphine analgesia in the rat formalin test, and to compare its effectiveness to that of dextroamphetamine (AMP). The formalin test was used because its long-lasting pain of moderate intensity resembles human clinical pain. Two different drug administration times were used to observe whether the early phase of the formalin response would be differentially affected by the drugs. At Drug Administration Time 1, rats received morphine 30 min prior to the formalin injection (-30 min) and MP or AMP 20 min prior to the formalin injection (-20 min). At Drug Administration Time 2, rats received morphine 10 min prior to the formalin injection (-10 min) and MP or AMP immediately prior to the formalin injection (0 min). All drugs were given subcutaneously. The results indicate that low doses of MP or AMP potentiate the analgesic effects of morphine. The clinical value of these drug combinations merits further investigation in animals and in humans.