Systemic administration of nitroglycerin (NTG) consistently provokes spontaneous-like migraine attacks in migraine sufferers, and in rat it induces hyperalgesia and allodynia. In the present study we modeled migraine headache by intraperitoneal (i.p.) injection of a single dose of NTG, which produced widespread thermal allodynia and mechanical hyperalgesia, photophobia, and increased anxiety-like behaviors and serum concentration of cortisol. Results suggest that the effects of NTG can be largely reversed by administration of ghrelin, which mimics the effects of sumatriptan used as relevant positive therapeutic control in this study. These findings suggest that ghrelin may alleviate some of the negative emotional states associated with migraine and may hold therapeutic potential in treating migraine headache.