The development of morphine tolerance and dependence in rats with chronic pain.

The development of tolerance and dependence to morphine injected onto the spinal cord was examined in a model of chronic pain following spinal cord injury in rats. Intrathecal morphine completely relieved the marked pain-like response of these rats to innocuous mechanical stimuli. The analgesic effect of morphine injected twice daily was, however, diminished within a few days. Tolerance to the antinociceptive effect of morphine assessed with the tail flick test also developed similarly in rats with chronic pain and in normal controls. Both groups exhibited similar signs of naloxone-precipitated withdrawal after 3 weeks of morphine treatment. The results suggest that the presence of chronic pain-like behavior did not prevent the development of morphine tolerance and dependence, even when morphine was used to treat the chronic pain itself.