Aim: Analgesic effect of morphine has been shown for many years. It has been also reported that blockade of potassium and calcium channels can induce analgesic effects in laboratory animals. Considering side effects of morphine such as addiction, using safe substitutions for morphine is a great interest for relieving severe pain. On the other hand, it has been reported that diabetic animals show hyperalgesia in compare to non-diabetic animals. Therefore, it is possible that pain signals may differently process in diabetic-animals due to the adverse effects of diabetes. In the present study possible interaction between analgesic effect of morphine and blockade of potassium and calcium channels was investigated in diabetic mice. Material and methods: A hot plate test of analgesia was used to assess analgesic effect of drugs in male NMRI mice. Drugs were used included morphine sulphate as a opioid agonist (Temad, Tehran, Iran), glibenclamide as a ATP-sensitive potassium channel blocker, nimodipine as a calcium channel blocker (both were gifts from Tocris, Bristol, UK), and alloxan monohydrate as a diabetes inducer (Sigma, USA). All drugs were injected through an intraperitoneal route. For induction of diabetes a dose of 200 mg/kg of alloxan was injected for three consecutive days, and fasting blood sugar level of 11 mmol/lit at 72 hour after the final injection was considered as a diabetic level. On the test day, morphine was injected 30 min before testing, while glibenclamide and nimodipine were injected 40 min prior to the test. Results: The results showed that morphine at doses of 10 and 15 mg/kg, induced analgesic effect in both non-diabetic and diabetic mice, but analgesic effect of morphine were decreased in diabetic mice. Injections of an ATP-sensitive potassium channel blocker, glibenclamide (4, 8, 12, 20 mg/kg) had no effect in non-diabetic mice, while at dose of 20 mg/kg induced an analgesic effect in diabetic mice. In addition, blockade of calcium channels u
