title: Odour-induced analgesia mediated by hypothalamic orexin neurons in mice.
abstract: Various folk remedies employ certain odorous compounds with analgesic effects. In fact, linalool, a monoterpene alcohol found in lavender extracts, has been found to attenuate pain responses via subcutaneous, intraperitoneal, intrathecal, and oral administration. However, the analgesic effects of odorous compounds mediated by olfaction have not been thoroughly examined. We performed behavioural pain tests under odourant vapour exposure in mice. Among six odourant molecules examined, linalool significantly increased the pain threshold and attenuated pain behaviours. Olfactory bulb or epithelium lesion removed these effects, indicating that olfactory sensory input triggered the effects. Furthermore, immunohistochemical analysis revealed that linalool activated hypothalamic orexin neurons, one of the key mediators for pain processing. Formalin tests in orexin neuron-ablated and orexin peptide-deficient mice showed orexinergic transmission was essential for linalool odour-induced analgesia. Together, these findings reveal central analgesic circuits triggered by olfactory input in the mammalian brain and support a potential therapeutic approach for treating pain with linalool odour stimulation.
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.|Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.|Department of Biochemical and Nutritional Chemistry, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Sodemi
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takaramachi, Ishikawa 920-8640, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Biochemical and Nutritional Chemistry, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Kajiya
authors.affiliation: Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanmura
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwaki
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kashiwadani
mesh_terms: D000080462:Acyclic Monoterpenes; D000698:Analgesia; D000818:Animals; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D039821:Monoterpenes / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D055696:Olfactory Perception; D000068797:Orexins / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D000068797:Orexins; C018584:linalool