Aims: To determine whether noxious stimulation of the rat tooth pulp induces learning and memory impairment through the induction of apoptosis in the hippocampus. Methods: Thirty-five adult rats were divided randomly into five groups (each n = 7) as follows: control, sham-operated, sham-vehicle, capsaicintreated, and capsaicin plus ibuprofen-treated group. After preparing dental cavities via cutting 2 mm of the distal extremities of the mandibular incisors, polyethylene crowns were placed on the teeth. Based on the study groups, different injections were administered into the cavities. Nociceptive scores for each block were obtained by measuring the number of seconds that the animal spent rubbing and flicking the lower jaw. After recording the nociceptive behaviors, spatial learning and memory were assessed by using the Morris Water Maze (MWM) test. The hippocampal levels of Bcl-2, Bax, and caspase-3 protein were determined by immunoblotting. Statistical analyses were performed using one- or two-way analysis of variance. Results: Noxious pulp stimulation induced by intradental application of capsaicin significantly increased time and traveled distance in the MWM test. Capsaicin stimulation of the pulp also significantly increased the Bax:Bcl-2 ratio and activated caspase-3 in the hippocampus (P .01), which was inhibited by ibuprofen pretreatment (P .05). Conclusion: Memory and learning impairment induced by noxious stimulation of the rat tooth pulp may be correlated with activation of apoptotic pathways in the hippocampus. Keywords: apoptosis, capsaicin, hippocampus, learning and memory, tooth pulp