He Min, Chen Ye-Xiang, Feng Pei-Pei, Chen Jie, Xu Chi, Zhou Shu-Ting, Liu Bo-Yu, He Xiao-Fen, Shao Xiao-Mei, Fang Jian-Qiao, Shen Zui, Liu Jing-Gen
Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Department of Acupuncture and Moxibustion, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Commun Biol. 2024 Dec 19;7(1):1651. doi: 10.1038/s42003-024-07372-2.
Chronic pain is often accompanied by anxiety, and gradually increasing anxiety makes the pain itself more protracted. Berberine has been found to be able to cross the blood-brain barrier to treat psychiatric disorders, but its neurocirculatory mechanisms remain unclear. Here, we found that neurons in cingulate area 2 (Cg2) of the caudal anterior cingulate cortex (cACC), but not in Cg1 of the cACC, projected to the ventral lateral thalamus (VLT). Next, we induced chronic inflammatory pain by plantar injection of complete Freund's adjuvant (CFA) and observed stable anxiety-like behaviors until two weeks postinjection. We specifically activated VLT-projecting cACC (Cg2) neurons in one-week-old CFA-induced mice without anxiety-like behaviors and in normal control mice to induce anxiety-like behaviors. We inhibited the activation of VLT-projecting cACC (Cg2) neurons in two-week-old CFA-treated mice with anxiety-like behaviors and observed that their anxiety-like behaviors were alleviated. On this basis, we further screened the effective dose of berberine for anxiolysis in two-week-old CFA-treated mice. We observed that the effective dose of berberine obtained above decreased the activity of VLT-projecting cACC (Cg2) neurons. The activation of VLT-projecting cACC (Cg2) neurons abrogated the anxiolytic effect of berberine in two-week-old CFA-treated mice.
慢性疼痛常伴有焦虑，而逐渐加重的焦虑会使疼痛本身更加迁延不愈。已发现黄连素能够穿过血脑屏障治疗精神疾病，但其神经循环机制仍不清楚。在此，我们发现，尾侧前扣带回皮质（cACC）的扣带2区（Cg2）的神经元，而非cACC的扣带1区（Cg1）的神经元，投射至腹外侧丘脑（VLT）。接下来，我们通过足底注射完全弗氏佐剂（CFA）诱导慢性炎性疼痛，并观察到在注射后两周内出现稳定的焦虑样行为。我们特异性激活一周龄CFA诱导的无焦虑样行为小鼠以及正常对照小鼠中投射至VLT的cACC（Cg2）神经元，以诱导焦虑样行为。我们抑制两周龄有焦虑样行为的CFA处理小鼠中投射至VLT的cACC（Cg2）神经元的激活，并观察到它们的焦虑样行为得到缓解。在此基础上，我们进一步筛选了黄连素在两周龄CFA处理小鼠中的抗焦虑有效剂量。我们观察到，上述获得的黄连素有效剂量降低了投射至VLT的cACC（Cg2）神经元的活性。在两周龄CFA处理小鼠中，投射至VLT的cACC（Cg2）神经元的激活消除了黄连素的抗焦虑作用。
