Diabetes Increases the Analgesia and Tolerance to Morphine in Acute Pain, but Not in Chronic Pain, While it Attenuates the Dependency in Rats

hanges in the concentration of either brain or blood glucose level appear to modulate antinociceptive and basal nociceptive processes. There are some contradictory data about the effect of diabetes on morphine antinociception. In this study the effects of alloxan-induced diabetes on morphine analgesia, tolerance and dependency were investigated, with a view to clarify the contradictions. Materials and Methods: Experimental diabetes was induced by a single injection of alloxan (120 mg/kg S.C.) in rats. Administration of morphine sulfate (7mg/kg i.p., 5 days) developed tolerance in animals. Acute and chronic pain in morphine treated diabetic and non-diabetic animals were evaluated using hot-plate and formalin tests respectively. In tolerant animals withdrawal signs (jumping, chewing, urine and feces) were recorded for ten minutes by the use of naloxone (2mg/kg i.p.). Results: Our results show that in the acute pain model, the antinociceptive effect of a morphine single dose was significantly enhanced (P < 0.001) in the diabetic group as compared to nondiabetic rats whereas, in diabetic tolerant rats in comparison with the non-diabetic tolerant ones morphine analgesia was extremely reduced (P<0.001). In the chronic pain model after a single dose administration, the only antinociceptive potency of morphine was enhanced (P<0.05) in the early phase, whereas after the induction of tolerance it was markedly reduced (P<0.01) in the early phase; was slightly enhanced (P<0.05) in the late phase in the diabetic rats compared to the non-diabetics. The withdrawal signs were significantly decreased (P<0.001) in the diabetic compared to the non-diabetic animals. Conclusion: It appears that the effects of hyperglycemia on pain thresholds differ in specific regions, using different tests and by duration of diabetes. Thus during the progress of diabetes, hyperglycemia might diminish the analgesic effect of morphine, blunt the development of dependency and alter the induction of tolerance.