Effect of Pantoprazole, a Proton Pump Inhibitor, on Morphine Tolerance in Rats

Pantoprazole's neuroprotective effects and its role in altering processes linked to apoptosis, inflammation, and oxidative stress were demonstrated. Consequently, this study aimed to explore how pantoprazole influences the development of morphine tolerance and the associated mechanisms, including apoptosis, oxidative stress, and inflammation. Six groups of rats were created: saline, 10 mg/kg pantoprazole, 5 mg/kg morphine, morphine tolerance, morphine + pantoprazole, and morphine tolerance + pantoprazole. Hot plate and tail-flick tests were utilized to detect the analgesic effect. Following the analgesic tests, samples of the dorsal root ganglion (DRG) tissues were collected. Oxidative stress parameters (total oxidant status, total antioxidant status), inflammation parameters (Pro-IL-1 beta, IL-1 beta, NLRP-3), and apoptosis proteins (Caspase-1, Caspase-3, Capsape-9) were detected in dorsal root ganglions (DRG) tissues. Pantoprazole showed a weak but statistically significant analgesic activity when given alone. Furthermore, pantoprazole potentiated the antinociceptive effect of morphine and prevented the development of tolerance to morphine. Moreover, it increased total antioxidant status and decreased total oxidant status as well as caspase-1 when given with single-dose morphine and after tolerance induction. Furthermore, pantoprazole decreased Pro-IL-1 beta, IL-1 beta, Caspase-3 and Capsape-9 levels after tolerance development. Collectively, pantoprazole produces a weak analgesic activity and boosts the morphine's analgesic effect. On the other hand, pantoprazole can prevent tolerance development. These effects likely arise through the modulation of pathways associated with oxidative stress, inflammation and apoptosis pathways.