Evaluation of the effect of chronic troxerotin administration on tolerance to morphine analgesic effects in male rats

Abstract

Introduction: The efforts to reduce pain have a long history. Over time, different tribes tried different methods to relief and eliminate pain. Today, opioids are widely used to treat severe pain. The long-term use of opioid analgesics is limited due to the development of tolerance as their adverse effects.Chronic abuse of morphine leads to physical and psychological dependence. Chronic use of morphine causes tolerance to its analgesic effects.Physical dependence on morphine appears with specific symptoms, as a result, the patient is forced to receive higher doses of morphine or to substitute a stronger opioid. Sometimes, due to the occurrence of tolerance, the two mentioned solutions do not produce the desired analgesic effect. One of the causes of tolerance to morphine is the production of inflammatory cytokines. It was observed that troxerotin has effects on inflammatory processes.Objective: Troxeration or vitamin P4 is a derivative of rutin bioflavonoid. Troxerotin has antioxidative, anti diabetic, anti-carcinogenic, fibrinolytic and anti-inflammatory effects. Troxerotin is safe even at high doses. The aim of this study is to investigate the effect of chronic troxerotin administration on tolerance to the analgesic effects of morphine.Method: The studied samples were adult male Wistar rats in the range of weight 270-225 g which were studied in 4 groups, each of them includes eightrats.These groups included: Morphine + saline control group and groups receiving three different doses of troxerotin with morphine.Results: According to the results obtained based on the current study, it showed that troxerotin in doses of 50 and 100 mg/kg had the most positive effects on reducing the tolerance duration to the analgesic effect of morphine.Conclusion: Due to its antioxidative effects, troxerotin reduces the tolerance to the analgesic effect of morphine. But since troxerotin has various functional mechanisms in the body, these effects are probably not dose- dependen.