Evaluation the effects of chronic intraperitoneal administration of methanolic extract of rhizome of Eremostachys azerbaijanica on the development of tolerance to morphine analgesia in male rats

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. In this study, to investigate the association between the effects of Eremostachys azerbaijanica and the incidence of opioid tolerance, chronic intraperitoneal administration of methanolic extract of rhizome that containing anti-inflammatory and antioxidant effects was used. Aim: The aim of this study was to investigate the effects of chronic intraperitoneal administration of methanolic extract of rhizome of Eremostachys azerbaijanica on development of tolerance to analgesic effect of morphine in male rats. Method: Ground rhizomes of E.azerbaijanica were Soxhlet extracted respectively with n-hexane, DCM and MeOH (1.1 L each). Six male rat groups were studied in this study, which included: the group received morphine (10mg/kg) + vehicle (1ml/kg, normal saline), morphine + three different doses of E.azerbaijanica extract (100, 200, 400mg/kg), the most effective dose of E.azerbaijanica extract (400mg/kg) with normal saline and the group that received normal saline. At the beginning, after determining the base latency time, half an hour after intraperitoneal injection of drugs, a hot plate test was performed every other day. Result: In the group receiving morphine and the group receiving vehicle and morphine, tolerance was occurred on day 9 and in the groups receiving different doses of E.azerbaijanica extract (100, 200, 400 mg/kg) with morphine; tolerance was occurred on days 13, 11 and 13 respectively. Serologic malondialdehyde levels were lower in the groups that receiving the most effective dose of the extract than the morphine group and showed a significant difference (p <0.05). Conclusion: Methanolic extract of rhizome of Eremostachys azerbaijanica, significantly delayed the development of tolerance to the analgesic effect of morphine (p<0.05).