Investigating the effects of pantoprazole on morphine-induced tolerance in mice

Abstract

Introduction: Chronic use of opioid leads to development of tolerance to their analgesic effects. The reasons for this tolerance are increase in inflammatory factors and gene expression of P-glycoprotein (P-gp). In some studies, it has been reported that pantoprazole inhibits P-gp gene expression and/or P-gp protein itself.Aim: The objective of this study was to evaluate the effects of pantoprazole on morphine-induced tolerance in male albino Swiss mice. Materials and methods: 80 male mice (20-30g) were randomly divided into two treatment and prevention main groups. Each main group was further divided into five subgroups, containing 8 mice each. Group A (treatment) received Saline or Morphine for 11 days and after that they received pantoprazole (25, 50, 100 mg/kg/day) on the day 11th. Group B (prevention) received Saline or Morphine and different doses of pantoprazole half an hour before the injection of morphine (10 mg/kg, sc) for 10 days.Then, on the day 11th, after taking the baseline latency time, by injecting a dose of morphine (mg/kg, ip, morphine analgesic) hot plate test was performed in the mentioned groups. Findings: The results indicated that different doses of pantoprazole (25, 50, 100 mg/kg/day) cause a significant reduction in the development of tolerance. Moreover pantoprazole treatment reduced tolerance to the analgesic effects of morphine.Conclusion: Pantoprazole not only prevents tolerance to the analgesic effects of morphine, but also restores the established tolerance in mice. This effect is probably due to the mechanism of inhibiting P-glycoprotein and its gene expression. Further studies must be designed to clarify the exact mechanisms.