Odor-induced Analgesia involving descending orexinergic inhibition in mice
Hideki Kashiwadani
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
In traditional remedies, mixtures of odorous compounds derived from plant extracts, have been used for their analgesic effects. Some odorous compounds have been identified as analgesics, such as salicylate, which emits a cold compress-like odor and was first identified in willow (Salix Alba) extracts. However, the analgesic effects of odorous compounds mediated by olfaction have not been well studied. Our research involved behavioral pain tests under odor exposure and demonstrated that linalool, a monoterpene alcohol found in lavender extract, has significant analgesic effects. These effects disappeared in anosmic model mice, indicating that the effects were triggered by olfactory sensory input evoked by linalool odor exposure. Further, we revealed the essential contribution of orexin-producing neurons in the hypothalamus. Mice lacking orexin neurons or orexin peptide showed no linalool odor-induced analgesia, indicating the crucial role of orexinergic transmission. Additionally, the analgesia was prevented by intrathecal administration of an antagonist specific to the type-1 orexin receptor. As orexin neurons are predominantly localized in the hypothalamus, the results indicate that linalool odor exposure drives the intrinsic analgesic circuit involving descending orexinergic projection from the hypothalamus to the spinal cord. Our results support a potential therapeutic approach for treating pain with linalool odor and provide a valuable tool for assessing the neuronal circuits of higher olfactory centers using typical odor-induced physiological responses. I will also talk about recent works on odor-induced anxiolytic and anti-pruritic effects.
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