ATP-sensitive Potassium Channels and L-type Calcium Channels are Involved in Morphine-induced Hyperalgesia after Nociceptive Sensitization in Mice

INTRODUCTION We investigated the role of ATP-sensitive potassium channels and L-type calcium channels in morphine-induced hyperalgesia after nociceptive sensitization. METHODS We used a hotplate apparatus to assess pain behavior in male NMRI mice. Nociceptive sensitization was induced by three days injection of morphine and five days of drug free. On day 9 of the schedule, pain behavior test was performed for evaluating the effects of morphine by itself and along with nimodipine, a blocker of L-type calcium channels and diazoxide, an opener of ATP-sensitive potassium channels. All drugs were injected through an intraperitoneal route. RESULTS The results showed that morphine (7.5, 10 and 15 mg/kg) induced analgesia in normal mice, which was prevented by naloxone (1 mg/kg). After nociceptive sensitization, analgesic effect of morphine (10 and 15 mg/kg) was significantly decreased in sensitized mice. The results showed that nimodipine (2.5, 5, 10 and 20 mg/kg) had no significant effect on pain behavior test in either normal or sensitized mice. However, nimodipine (20 mg/ kg) along with morphine (10 and 15 mg/kg) caused more decrease in morphine analgesia in sensitized mice. Furthermore, diazoxide by itself (0.25, 1, 5 and 20 mg/kg) had also no significant effect on pain behavior in both normal and sensitized mice, but at dose of 20 mg/kg along with morphine (10 and 15 mg/kg) decreased analgesic effect of morphine in sensitized mice. DISCUSSION It can be concluded that potassium and calcium channels have some roles in decrease of analgesic effect of morphine after nociceptive sensitization induced by pretreatment of morphine.