Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (T_H2) 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^DMV) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral T_H2 immune response: glutamatergic neurons in the primary somatosensory cortex (Glu^S1HL)→ACh^DMV→spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABA^CeA)→ACh^DMV→spleen circuit. The acute pain condition elicits increased excitation from Glu^S1HL neurons to spleen-projecting ACh^DMV neurons and increased the proportion of splenic T_H2 immune cells. The chronic pain condition increased inhibition from GABA^CeA neurons to spleen-projecting ACh^DMV neurons and decreased splenic T_H2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen.

疼痛涉及神经免疫串扰，但其机制仍不清楚。在这里，我们表明，在患有急性和慢性神经性疼痛的雄性小鼠中，脾辅助 T 2 (TH _{2 ) 免疫细胞反应的调节存在差异，并且迷走神经背运动核 (ACh} ^DMV )中的乙酰胆碱能神经元直接支配脾脏。结合体内记录和免疫细胞分析揭示了以下两个不同的回路参与疼痛介导的外周 T _H 2 免疫反应：初级体感皮层中的谷氨酸能神经元 (Glu ^S1HL )→ACh ^DMV →脾回路和中央核中的 GABA 能神经元杏仁核 (GABA ^CeA )→ACh ^DMV →脾回路。急性疼痛引起 Glu ^S1HL神经元对脾脏投射 ACh ^{DMV神经元的兴奋增加，并增加脾脏 T} _H 2 免疫细胞的比例。慢性疼痛增加了 GABA ^CeA神经元对脾脏投射 ACh ^DMV神经元的抑制，并减少了脾脏 T _H 2 免疫细胞。因此，我们的研究证明了大脑如何编码脾脏中疼痛状态特异性的免疫反应。