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The development of tolerance to and dependence on morphine was studied in a model of experimental chronic pain in the rat (Freund's adjuvant-induced arthritis). Animals were rendered tolerant by subcutaneous implantation of 3 pellets of 75 mg morphine base each. Those pain-suffering rats developed tolerance to the analgesic effect of the alkaloid at a slower rate than control animals. Moreover, upon treatment with naloxone, these morphine-tolerant-dependent rats from the model, showed a lower incidence of several withdrawal symptoms, particularly jumping, chattering, ptosis, writhing, body shakes and squeaking on touch. These findings suggest that animals suffering from chronic pain present an altered physiological response to the continuous inhibitory effect of exogenous opioids. These differences do not seem to involve cAMP mediated mechanisms since 3-isobutyl-1-methylxanthine (IBMX) administration did not distinguish between control and arthritic rats.
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