Effect of simultaneous injection of l-arginine in dorsal hippocampus and laterodorsal periaqueductal gray matter on morphine-induced analgesia in rat’s formalin test

Background and Objective: Injection of l-arginine, a precursor of nitric oxide, in the rat’s hippocampus or periaqueductal gray matter reduces the analgesic effect of morphine on formalin-induced pain, but the effect of simultaneous injection of the substance in both areas have not been shown as our purpose of this research. Materials and Methods: Wistar rats were used as control, morphine, and l-arginine groups. The rats were simultaneously cannulated in two areas of the dorsal hippocampus and laterodorsal PAG. One week later, the control animals received 50 μl of 2.5% formalin in the paw of the left foot under restrainer. The morphine group 10 min before formalin received the opioid (6 mg/kg, intraperitoneally). Other groups took l-arginine (0.25-2 μg/rat) in only one area (d hippocampus or ld PAG), prior to morphine administration. The effective dose of l-arginine (0.5 μg/rat) simultaneously was injected in both areas. The findings were analyzed by analysis of variance (ANOVA) under α=0.05. Results: Morphine induced analgesic response. Injection of NO precursor both separately and simultaneously in the two nuclei reduced morphine-induced analgesia. Conclusion: Increasing levels of NO due to exclusive or concurrent injection of l-arginine in the areas likely antagonize the morphine response.