THE DEVELOPMENT OF OPIOID TOLERANCE IN THE FORMALIN TEST IN THE RAT

The formalin test produces persistent pain in animals and is believed to provide a better model of the pain experienced by humans than do te sts that measure reflex nociceptive thresholds. The present study eval uated whether tolerance to morphine develops in the formalin test in t he rat. Morphine (75 mg) or vehicle pellets were implanted subcutaneou sly for 5 consecutive days. On the 6th day, a subcutaneous (s.c.) dose of either morphine (10 mg/kg) or saline was given 30 min prior to the injection of 50 mu l of 5% formalin into the left hindpaw of the rats . In vehicle-pelleted rats administered saline, formalin evoked charac teristic pain behavior consisting of licking, biting and flinching of the affected hindpaw. The pain behavior in morphine-tolerant rats give n morphine did not differ significantly from the saline control; i.e., tolerance to the analgesic effect of morphine was demonstrable in the formalin test. These results do not agree with previous published rep orts. Rather, these results suggest that the mechanisms involved in mo rphine analgesia in the formalin test and in reflex nociceptive tests are similar and subject to the same problem of tolerance with chronic opioid administration.