将来自英国生物银行的人类神经成像与啮齿动物模型相结合，小组发现了双相海马重塑。海马体积在早期疼痛阶段增加，与认知改善相矛盾，但在共病抑郁症中下降。在啮齿类动物中，齿状回（DG）作为控制这种转变的枢纽：DG的病变阻止了情感症状。DG活性升高与新生儿神经元过度活跃、小胶质细胞募集和重塑有关，从而导致回路失衡。抑制新生神经元活动以认知为代价减轻情绪病理，而小胶质细胞调节选择性地恢复情感行为而不以认知为代价。这些发现揭示了小胶质细胞介导的海马重塑是连接慢性疼痛和情绪障碍的关键机制。
据了解，慢性疼痛常常演变为抑郁和焦虑，但感觉痛苦与情感功能障碍之间的联系机制尚不清楚。
附：英文原文
Title: From chronic pain to depression: Neurogenesis-driven microglial remodeling in the hippocampal dentate gyrus
Author: Ming Ding, Shitong Xiang, Yuqing Zhang, Lei Wei, Yuanfeng Weng, Xueting Zhang, Yiling Ni, Yuwen Zhang, Qianfeng Wang, Ruiqing Hou, Huaihao Du, Ka Kei Chio, Wei Zhang, He Wang, Tianye Jia, Yi Wu, Jianfeng Feng, Trevor W. Robbins, Xiao Xiao
Issue&Volume: 2026-03-19
Abstract: Chronic pain often evolves into depression and anxiety, yet mechanisms linking sensory distress to affective dysfunction remain unclear. Integrating human neuroimaging from the UK Biobank with a rodent model, we uncovered biphasic hippocampal remodeling. Hippocampal volume increased during early pain stages, with paradoxical cognitive improvements, but declined with comorbid depression. In rodents, the dentate gyrus (DG) acted as a hub governing this transition: Lesions of DG prevented affective symptoms. Elevated DG activity was linked to hyperactive newborn neurons and microglial recruitment and remodeling, leading to circuit imbalance. Whereas suppressing newborn neuron activity alleviated emotional pathology at the expense of cognition, microglial modulation selectively restored affective behavior without cognitive cost. These findings reveal microglia-mediated hippocampal remodeling as a key mechanism linking chronic pain to mood disorders.
DOI: aee6177
Source: https://www.science.org/doi/10.1126/science.aee6177