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.

Analgesic-Like Activity of Essential Oil Constituents: An Update

“…A study by Tashiro and collaborators [ 65 ] reported the antinociceptive effect of linalool in a different experimental protocol using vapour exposure mediated by hypothalamic orexin neurons, one of the main mediators in the behavioral responses to pain [ 66 ]. The involvement of these cells was evidenced by a significant increase in the number of c-Fos-expressing orexin neurons, and in linalool odour-exposed and odourless air-exposed orexin neuron-ablated mice that exhibited similar pain behavior in the first and second phase of the formalin test.…”

“…In the investigation of the participation of olfactory processing in linalool analgesic effects by chemical nociceptive stimulus (formalin test), pain behavior in olfactory bulbectomized mice under linalool vapour exposure did not differ markedly from the odourless air group in both phases of the test. In the anosmic model using mice with a nonfunctional olfactory epithelium, no effects of linalool vapour were observed, providing further evidence that the olfactory response produced by linalool vapour may play a key role in inducing analgesic effects [ 65 ].…”

Linalool Odor-Induced Anxiolytic Effects in Mice

“…In control group, 10 mL/kg of corn oil was administered by intraperitoneal injection in control group. Two weeks after the injection, 3-MI treated mice were used for the behavioral test (Tashiro et al, 2016 ).…”

Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms

“…Though no study has investigated its effect independently in neuropathic pain models, animal social enrichment alone has been demonstrated to reduce the duration of inflammatory pain . Of note, EE studies on inflammatory, thermal, or muscle pain models used a greater variety of stimulations, such as odor, tactile, or animal handling, but it is beyond the scope of our review. It is anticipated that a more diverse range of EE modalities will be tested in future studies.…”