In folk remedy, it has long been believed that some odorous compounds have analgesic effects. Actually several odorous molecules affect the central or peripheral tissues pharmacologically and show the analgesic effects. However, it has not yet fully revealed whether "the odor", or the sense of smell, could really induce the analgesia. To address the question, we first performed the hot plate test and the formalin test under the odor exposure in wild type mouse. Among several odor molecules examined, we found an odor molecules ("odorant X") showed significant analgesic effect. Next, to examine whether the olfactory input trigger the analgesic effect, we performed the formalin test under odorant X exposure in olfactory deprived mouse. In bulbectomized mice whose main olfactory bulbs were bilaterally suctioned, the odorant X exposure-induced analgesic effects were disappeared. Olfactory epithelium deprived mice whose olfactory sensory neurons were removed by 3-methylindole i.p. administration neither showed the analgesic effects. These results indicated that olfactory input trigger the odorant X-induced analgesic effects. Next to address the central neuronal circuits underlying the odor-induced analgesic effects, we focused on the hypothalamic orexinergic neurons which play pivotal role for pain modulation. In orexinergic neuron ablated mice, the odor-induced analgesic effects were completely abolished. In addition, orexin peptide depleted mice lost the analgesic effects. These result indicated that hypothalamic orexinergic neurons mediated the odor-induced analgesic effects. In conclusion, we found the odor-induced analgesic effect mediated by the hypothalamic orexinergic neurons in mouse. Our findings suggest that odor input could modulate the pain processing by driving the intrinsic analgesic circuits including hypothalamic orexinergic neurons.