Analgesia produced by low doses of the opiate antagonist naloxone in arthritic rats is reduced in morphine-tolerant animals.

In a model of experimental chronic pain (adjuvant-induced arthritic rats), low doses of the opiate antagonist naloxone produced a profound analgesia. Maximum analgesia was seen with 3 micrograms/kg (i.v.). In contrast, hyperalgesia was obtained with much higher doses (1-3 mg/kg, i.v.). The hyperalgesic effects were not affected in arthritic animals rendered tolerant to morphine, but the paradoxical analgesic effects were significantly reduced. This decrease suggests that naloxone analgesia involves interaction with opiate receptors and that the operation of endorphinergic systems differs in normal animals and animals which experience persistent pain.