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, P. R. China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, P. R. China.
Nat Neurosci. 2024 Mar;27(3):471-483. doi: 10.1038/s41593-023-01561-8. Epub 2024 Jan 30.
Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (T2) immune cell response is differentially regulated in male mice with acute versus chronic neuropathic pain and that acetylcholinergic neurons in the dorsal motor nucleus of the vagus (ACh) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral T2 immune response: glutamatergic neurons in the primary somatosensory cortex (Glu)→ACh→spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABA)→ACh→spleen circuit. The acute pain condition elicits increased excitation from Glu neurons to spleen-projecting ACh neurons and increased the proportion of splenic T2 immune cells. The chronic pain condition increased inhibition from GABA neurons to spleen-projecting ACh neurons and decreased splenic T2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen.
疼痛涉及神经免疫相互作用，但其中的机制尚不清楚。在这里，我们表明，在急性和慢性神经性疼痛的雄性小鼠中，脾脏辅助性 T2（T2）免疫细胞反应受到不同的调节，并且迷走神经背核中的乙酰胆碱能神经元（ACh）直接支配脾脏。结合体内记录和免疫细胞分析，揭示了参与疼痛介导的外周 T2 免疫反应的两个不同的回路：初级躯体感觉皮层中的谷氨酸能神经元（Glu）→ACh→脾脏回路和杏仁核中央核中的 GABA 能神经元（GABA）→ACh→脾脏回路。急性疼痛条件会增加来自 Glu 神经元到投射到脾脏的 ACh 神经元的兴奋，并增加脾脏 T2 免疫细胞的比例。慢性疼痛条件会增加来自 GABA 神经元到投射到脾脏的 ACh 神经元的抑制，并减少脾脏 T2 免疫细胞。因此，我们的研究表明了大脑如何在脾脏中对疼痛状态特异性免疫反应进行编码。
