Background and Objective: Opioid-induced hyperalgesia is a state of nociceptive sensitization which is induced by repeated exposure to opioids and is believed to be different from tolerance in some aspects. This response limits the utility of opioids, as well as our ability to control chronic pain. Mechanisms of opioid-induced hyperalgesia remains to be understood. ATP-dependent potassium (KATP) channels are involved in some actions of morphine. Therefore, the aim of this study was to examine possible involvement of KATP channels in opioid-induced hyperalgesia. Method: We used male NMRI mice in these experiments. Opioid-induced hyperalgesia was established under a regimen of morphine treatment including injections of morphine 20 mg/kg, i.p. twice per day on days 1–3 and 40 mg/kg twice per day on day 4. Opioid-induced hyperalgesia was assessed on day 5 with a hotplate test of analgesia after injections of different doses of morphine (0, 2.5, 5 and 10 mg/kg). Then, effects of diazoxide, an opener of KATP channels and glibenclamide, as a blocker of KATP channels on opioid-induced hyperalgesia on day 5 were examined. Result: The results showed that opioid-induced hyperalgesia was established with the regimen of four days injections of morphine as revealed by decreases in antinociception of different doses of morphine on hotplate test. Diazoxide at dose of 5 mg/kg and glibenclamide at dose of 10 mg/kg along with morphine 10 mg/kg prevented, at least partly, the hyperalgesia induced by the opioid. Conclusions: In can be concluded that KATP channels have modulatory effects in induction of morphine-induced hyperalgesia.
