BACKGROUND Pain is one of the most common problems in clinical medicine. There is considerable evidence that pharmacologic approaches are the most widely used therapeutic options to ameliorate persistent or chronic pain. In this study it was evaluated the effect of l-NAME and naltrexone in the antinociception induced by administration of gabapentin in the orofacial formalin test of mice. METHODS The algesiometer assay was performed by the administration of 20 μl of 2% formalin solution injected into the upper right lip of each mouse. RESULTS The dose of gabapentin that produces the 50% of the maximum possible effect (ED50) was significantly increased by the pretreatment with l-NAME or naltrexone. CONCLUSIONS These results suggest that gabapentin produce antinociception partly via the activation nitridergic pathways and opioid system.