浙江中医药大学徐驰小组的研究显示，CXCR2通过调节腹侧齿状回成年神经发生调节小鼠慢性疼痛共病性抑郁。这一研究成果于2025年2月19日发表在国际顶尖学术期刊《中国药理学报》上。

在这项研究中，课题组研究了神经干细胞（NSCs）在腹侧DG中的CXCR2在调节慢性神经性疼痛小鼠的AHN和抑郁样行为中的作用。备用神经损伤（SNI）手术诱导小鼠慢性神经性疼痛；监测机械异常性痛和抑郁样行为，然后收集小鼠DG进行分析。小组观察到，慢性神经性疼痛通过抑制NSCs的神经元分化，显著减少腹侧DG中未成熟神经元的数量；通过向DG中注射腺相关病毒（AAV），在NSCs中特异性过表达CXCR2，恢复SNI小鼠成年神经发生，并减轻抑郁样行为。相比之下，幼稚小鼠海马NSCs中CXCR2的敲低足以抑制成年神经发生，诱导抑郁样行为。

此外，研究小组发现SNI小鼠腹侧DG中的Wnt3a/β-catenin通路下调，在CXCR2过表达或向腹侧DG注入CXCR2激动剂CXCL1后，该通路恢复。研究团队得出结论，海马NSCs中表达的CXCR2对于调节成人神经发生和慢性疼痛诱导的抑郁样行为至关重要，它们代表了治疗慢性疼痛共病抑郁症的新靶点。

据介绍，研究表明，慢性疼痛可能通过损害成年海马神经发生（AHN）腹齿状回（DG）诱导抑郁样行为，而AHN的恢复可有效缓解抑郁。C-X-C基序趋化因子受体2 （CXCR2）是一种参与海马多种神经活动的趋化因子受体，包括AHN。

附：英文原文

Title: CXCR2 modulates chronic pain comorbid depression in mice by regulating adult neurogenesis in the ventral dentate gyrus

Author: Li, Xiao-jie, Wu, Shuo, Liu, Zi-han, Liu, An-an, Peng, Hui-sheng, Wang, Yu-jun, Chen, Ye-xiang, Liu, Jing-gen, Xu, Chi

Issue&Volume: 2025-02-19

Abstract: Research shows that chronic pain may induce depression-like behaviors through impairing adult hippocampal neurogenesis (AHN) in the ventral dentate gyrus (DG), whereas restoration of AHN may effectively alleviate depression. The C-X-C motif chemokine receptor 2 (CXCR2) is a chemokine receptor involved in various neural activities of the hippocampus including AHN. In this study we investigated the role of CXCR2 of neural stem cells (NSCs) in the ventral DG in regulating both AHN and depression-like behaviors of mice with chronic neuropathic pain. Chronic neuropathic pain was induced in mice by the spared nerve injury (SNI) surgery; mechanical allodynia and depression-like behaviors were monitored, then mouse DG was collected for analysis. We observed that chronic neuropathic pain significantly decreased the number of immature neurons in the ventral DG by inhibiting the neuronal differentiation of NSCs; specific overexpression of CXCR2 in NSCs by injecting the adeno-associated virus (AAV) into the DG restored adult neurogenesis accompanied by alleviated depression-like behaviors in SNI mice. In contrast, the knockdown of CXCR2 in hippocampal NSCs of naive mice was sufficient to inhibit adult neurogenesis, inducing depression-like behaviors. Moreover, we found that the Wnt3a/β-catenin pathway was downregulated in the ventral DG of SNI mice, which was restored after CXCR2 overexpression or infusing a CXCR2 agonist CXCL1 into the ventral DG. We conclude that CXCR2 expressed in hippocampal NSCs is crucial for regulating adult neurogenesis and chronic pain-induced depression-like behavior, thus representing a new target for the treatment of chronic pain comorbid depression.

DOI: 10.1038/s41401-025-01496-9

Source: https://www.nature.com/articles/s41401-025-01496-9