Background and Objectives: Opiodergic system has important role in pain control. Origanum vulgare is a folk medicine with analgesic properties which is widely distributed in the north and northwest parts of Iran. The mechanism of therapeutic effects of Origanum vulgare is not understood. The aim of this study was to evaluate the intervention effect of opioid agonist (morphine) and antagonist (naloxone) on analgesic effects of Origanum vulgare.

 Methods: In this study 28 Male Wistar rats (200-250 g) were used (n=7). The rats were anaesthetized by ketamine (80mg /kg) and xylazine (10mg /kg) and a cannula was inserted into the left ventricle according to atlas of Paxinos characteristics using stereotaxic apparatus. The animals were allowed to recover for 5-7 days .In pilot examination, the effective dose of ORG extract determined 3µg/rat i.c.v. Rats were divided into 4 groups:Control group given saline 0.5ml.i.p/ saline 5µl.i.c.v or ORG 3µg/rat.i.c.v. other groups are morphine (2mg/kg ,i.p) and ORG3µg/rat,i.c.v , Naloxone (1mg/kg,i.p) and ORG 3µg/rat,i.c.v. The latency response of rats to thermal stimulation was recorded (30, 45, 60, 75, 90 &120 min after treatment) by Tail flick test. Repeated Measurement test and ANOVA were used to determine significant differences.

 Results: There was significant decrease in the pain threshold following the co-administration of ORG extract with naloxone in the Tail flick test. There also was significant decrease in the latency response or pain threshold 90 and 120 min after intervention in naloxone group compared with that in control group (p< 0.05).

 Conclusion: The results of this study showed that analgesic effect of aqueous extract of Origanum vulgare may be mediated, at least in part, by opioidergic system.