Influence of antineoplastic drugs on morphine analgesia and on morphine tolerance

The possible influence of cisplatin, methotrexate, adriamycin and vincristi ne on thermal pain threshold, morphine analgesia and development of morphin e tolerance was investigated in mice. In the hot-plate test, the nociceptiv e threshold was not affected by acute or repeated administration of any of the antineoplastic drugs used. The analgesic activity of morphine was signi ficantly reduced by pretreatment with cisplatin, intraperitoneally (i.p.) i njected at the dose of 2 mg/kg. In contrast, methotrexate, subcutaneously ( s.c.) injected at the dose of 1 and 5 mg/kg, adriamycin (1 and 3 mg/kg s.c. ), vincristine (0.25 and 0.5 mg/kg i.p.) and a lower dose of cispratin (1 m g/kg i.p.) had no effect. The development of tolerance to morphine analgesi a was delayed by adriamycin but was not influenced by the other antineoplas tic drugs used. These data show that, of the four antineoplastic agents use d in this study, cisplatin may interfere in the mechanism of action of morp hine, and that adriamycin may delay the development of opiate tolerance. (C ) 1999 Elsevier Science B.V. All rights reserved.