Study on the effects of hydroalcoholic extract of Medicago sativa on the development of tolerance to morphine analgesia in rat

Abstract

Introduction: The long term use of opioid analgesics is limited due to the development of tolerance and their adverse effects. One of the reasons for the tolerance incidence to morphine is the activity of glial cells and the production of pro-inflammatory cytokines. The Medicago sativa (alfalfa) that used in this study contains compounds with anti-inflammatory and anti-oxidant effects. Aim: The aim of this study was to investigate the effects of Medicago sativa extract on the development of tolerance to the analgesic effect of morphine in male rats. Method: Hydro-alcoholic extract of Medicago sativa was prepared by maceration. Seven male rat groups were studied in this study, which included: the group received normal saline (1ml/kg), receiving morphine (10mg/kg), morphine + vehicle (1ml/kg, 30% Kolliphor® HS15 in normal saline), morphine + three different doses of the alfalfa extract (25, 50, 100mg/kg) and receiving only the most effective dose of the alfalfa extract according to this study (100mg/kg). In the beginning, after determining the base latency time, a hot plate test was performed every other day, half an hour after intraperitoneal injection of the drugs. Result: In the group receiving morphine and the group receiving vehicle and morphine, tolerance was occurred on the 7th day and in the groups receiving different doses of the extract (25, 50, 100 mg/kg) with morphine; tolerance occurred on days 11, 13 and 17 respectively. Malondialdehyde serum levels were lower in the groups receiving the most effective dose of the extract than the morphine group and showed a significant difference (p <0.001). Conclusion: Probably Medicago sativa extract due to its anti-inflammatory and anti-oxidant effects has decreased the rate of morphine tolerance (p <0.05). further studies are needed to better understand it.