The Role of ATP-Sensitive Potassium Channels and Opioid Receptors on Cimetidine Antinociception in Mouse

Recent studies have shown that cimetidine (CIM) induces antinociception after intracerebroventricular administration in mouse. It also has an anti-inflammatory effect, but the underlying mechanism of CIM effect is not clear. This study was designed to evaluate antinociception effect of CIM by intraperitoneal injection (ip) and the role of ATP- sensitive potassium channels and opioid receptors.

In this study 170 male mice (25-30g) were used. Tail flick model applied for evaluation the acute pain. The antinociception effect of CIM was studied by ip injection of 50 mg/kg and the role of opioid receptors was evaluated by subcutaneous administration of 2 mg/kg naloxone. The role of closing and opening effect of potassium channel in the antinociceptive effect of CIM were assessed by ip injection of minoxidil (2mg/kg) and glybenclamide (5mg/kg). The effect of CIM on the antinociceptive effect of morphine (5mg/kg) was also evaluated.

Our results showed that ip administration of CIM induces antinociception in Mice (p<0/05). Both Naloxone (mean 3.41) and Glybenclamide (mean 4.22) decreased the threshold of pain in mice (p=0.000), and minoxidil (mean 6.34) induced antinociception (p=0.003). However none of them had a significant effect on CIM antinociception (with the mean 8.14). Also antinociceptive effect of morphine was significantly potentiated in CIM treated group (p<0001).

Peripheral antinoceptive effects of CIM is not related to opioid receptor and ATP sensitive potassium Channels.