Evaluation of the effect of chronic administration of pirfenidone on the tolerance to the analgesic effects of morphine in male mice

Abstract

Introduction: The chronic use of opioids causes dependence and tolerance towards them, and various mechanisms such as oxidative stress and increased production of inflammatory factors are involved in this process; The antioxidant and anti-inflammatory effects of pirfenidone have been proven. Aim: The current study aimed to investigate the effect of chronic administration of pirfenidone on the tolerance to the analgesic effects of morphine in mice.Methods: The experiment was conducted in 6 groups of 8 mice, in first group, 8 mice were given two injections every day at interval of half an hour and each time 10 (ml/kg, i.p.) of normal saline, in second group, 10 (ml/kg) every day. kg, i.p) morphine and half an hour before that 10 (ml/kg, i.p) normal saline, in third group morphine (mg/kg, i.p 10) and half an hour before that 1 ml/kg containing pirfenidone DMSO (10%) and in other three groups, we injected three different doses of pirfenidone (25/50/100 mg/kg, i.p.) one hour before morphine. In all groups, we performed a hot plate test every other day for half an hour after the injections. Finally, blood was taken from all groups and TAC, MDA, TNF-a, IL-1, and IL-6 factors were analyzed. Results: In the group receiving vehicle and morphine on day 5 and in the groups receiving doses of 25, 50 and 100 mg/kg pirfenidone along with morphine on days 11, 11 and 3, respectively, tolerance was established, but only the dose of 25 mg/kg pirfenidone was significantly (P<0.05) delayed tolerance to morphine. Also, the level of inflammatory factor IL-6 showed a significant difference (P<0.001) only in the group receiving the pirfenidone (25 mg/kg) compared to the morphine group. Conclusion: Probably, pirfenidone (25 mg/kg) delayed the onset of tolerance to morphine due to its anti-inflammatory effects. We need more studies to understand it better.