MORPHINE FAILS TO PRODUCE TOLERANCE WHEN ADMINISTERED IN THE PRESENCEOF FORMALIN PAIN IN RATS

The present study examined the development of tolerance to morphine an algesia under conditions in which morphine was administered in the pre sence or absence of pain induced by subcutaneous injection of 50 mul o f 2.5% formalin into the hind paw of rats. Animals were injected with morphine (25 mg/kg, i.p.) or saline for 3 consecutive days either in t he presence of pain (10 min after formalin injection) or in the absenc e of pain (6 h prior to formalin injection). On the 4th day, tolerance to the analgesic effect of test doses of morphine (6 or 10 mg/kg) was assessed in the formalin and tail-flick tests, respectively. Signific ant tolerance in both tests was observed in animals receiving morphine in the absence of pain during the tolerance induction period, but not in animals receiving morphine in the presence of pain.