Activation of peripheral trigeminal fibers induces neurogenic inflammation in rat dura mater, as well as vascular and mat cell changes. These changes parallel an increase of vasodilating and permeability promoting peptides in venous effluent of the cephalic circulation. The experimental model of electrical trigeminal ganglion stimulation or systemic capsaicin administration has proven effective in detecting cellular activation in brainstem trigeminal nuclei. Animal experimental models of trigeminovascular activation and the effects of antimigraine drugs on functional and morphological consequences of such activation provide the background for further models and for developing pharmacological strategies in this field.