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.