The effect of alloxan-induced diabetes on anti-nociception and on the development of morphine tolerance and dependence in rats



Diabetes is one of the most common diseases in all societies including Iran. One of its important complications is the neuropathic pain, which can be relieved by opioid drugs such as morphine. Opioid therapy is restricted due to development of tolerance and physical or mental dependence. In this study, the effect of diabetes on morphine analgesia and development of morphine tolerance and dependence was investigated. Experimental diabetes was induced by alloxan (120 mg/kg, s.c.) in rats. Morphine sulfate (7 mg/kg, i.p.) application for 5 days developed tolerance in animals. On 5th day, 30 min after the injection of morphine, the acute and chronic pain was evaluated in diabetic and non-diabetic animals using hot plate and formalin test. In addition, withdrawal signs (jumping, chewing, urine and feces) were recorded for ten minutes using naloxone (2 mg/kg, s.c.). The results showed that the anti-nociceptive effect of morphine for acute pain markedly reduced, but slightly enhanced for chronic pain model. The withdrawal signs significantly decreased in diabetic animals. It seems that in diabetic state, an endogenous analgesic system is activated to potentiate the opioid effects. Further investigation is needed to clarify these mechanisms.