The Role of Formalin-Induced Pain in Morphine Tolerance, Withdrawal, and Reward

The effect of a commonly used experimental pain-induction procedure (formalin injection into a hindpaw site) on morphine tolerance, withdrawal, and reward was examined in rats. Results suggest that the effects of morphine are different in the organism that is experiencing pain at the time it receives the drug than in the organism that is pain free. The presence of pain at the time of each morphine administration decreased analgesic tolerance, decreased naloxone-precipitated withdrawal, and enhanced the rewarding effect of the opiate. These findings, together with those of previous studies, suggest that theories of opiate tolerance, withdrawal, and reward should incorporate the effects of pain.