Rapid development of tolerance to morphine in the formalin test

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Abstract
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.

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