Rapid development of tolerance to morphine in the formalin test.

Previous reports have suggested that tolerance to the antinociceptive effects of morphine does not develop in the formalin test. To re-examine these findings, morphine was administered via multiple injections or continuous infusion from 0 to 4 days prior to testing with either the formalin or tail-flick test. Following twice daily injections (5.0 mg kg-1 s.c.), significant tolerance developed within 2 days with the formalin test but not until day 4 with the tail-flick test. Significant tolerance was noted with both tests 4 days following the implantation of osmotic mini-pumps (10 mg kg-1 day-1, s.c.). We conclude that in mice, tolerance to the analgesic effects of morphine develops rapidly with the formalin test.