Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Key Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei 230032, China.
Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
Cell Rep. 2024 Oct 22;43(10):114800. doi: 10.1016/j.celrep.2024.114800. Epub 2024 Oct 3.
Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPir) innervate GABAergic neurons in the IC (IC) to inhibit local glutamatergic neurons (IC) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPir→IC pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPir neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain.
薰衣草精油（LEO）已被证明可以缓解人类的疼痛，但潜在的神经机制尚不清楚。在这里，我们发现，通过激活来自梨状前皮层（aPir）到岛叶皮层（IC）的投射，吸入 0.1%的 LEO 可以在完全弗氏佐剂（CFA）诱导的炎性疼痛的小鼠中产生镇痛作用。具体来说，体内光纤光度记录和病毒追踪数据表明，来自 aPir（aPir）的谷氨酸能投射支配 IC（IC）中的 GABA 能神经元，从而抑制在炎性疼痛中过度激活的局部谷氨酸能神经元（IC）。该 aPir→IC 通路的光遗传学或化学遗传学激活可以重现 LEO 吸入在 CFA 小鼠中的镇痛作用。相反，人工抑制投射到 IC 的 aPir 神经元会消除 LEO 诱导的镇痛作用。因此，我们的研究描绘了一个 LEO 反应性嗅觉系统回路机制，通过 aPir→IC 神经连接来缓解炎性疼痛，为开发基于香气的治疗方法缓解疼痛提供了证据支持。
