The anti-nociceptive effects induced by aromatic compounds derived from plant explants have attracted pharmacologists as the seeds of drug discovery. For example, salicylic acid was originated in the extract of White Willow (Salix Alba). However, most of the effects were purely brought by the direct interaction of the compounds with functional molecules in our body, thus the effects are independent of their odor. Then, are there any functional benefits of "odor" for anti-nociception?

To address the question, we performed pain-related behavior tests under odor exposure in mice. We found that the odor of linalool, one of the terpene-alcohol found in lavender extract, induced significant analgesic effects. The effects disappeared after olfactory deprivation, indicating that the olfactory input evoked by linalool odor triggers the effects. Interestingly, the effects were not observed in mice lacking Orexin peptides, which are produced by hypothalamic neurons, indicating the pivotal role of the orexinergic transmission for the effects. Furthermore, the intrathecal injection of orexin 1 receptor selective antagonist canceled out the effects, indicating the contribution of the orexinergic descending inhibitory pathway in the analgesic effects. These findings set up the neuronal circuit mechanisms underlying the odor-induced analgesia.