苏州大学徐广银研究小组取得一项新突破。他们揭示了谷氨酸能VTA神经元NR2A的上调与雄性小鼠慢性内脏疼痛有关。该研究于2025年4月28日发表于国际一流学术期刊《神经科学通报》杂志上。

慢性内脏疼痛是由内脏器官及其相关神经通路的功能障碍或敏感引起的一种持续性和衰弱性疾病。越来越多的证据表明，中枢神经系统功能的不平衡在内脏疼痛的进展中起着至关重要的作用，但神经回路和分子靶点的确切机制仍未得到充分研究。

在本研究中，腹侧被盖区（VTA）被证明介导内脏疼痛小鼠。内脏疼痛刺激增加了谷氨酸能VTA神经元的c-Fos表达和Ca²⁺活性，谷氨酸能VTA神经元的光遗传调节改变了内脏疼痛。特别是，VTA内NMDA受体2A （NR2A）亚基的上调导致小鼠内脏疼痛。选择性NR2A抑制剂可减少内脏疼痛诱导的c-Fos阳性神经元的数量，减轻内脏疼痛。药理学结合化学遗传学进一步证实，谷氨酸能VTA神经元基于NR2A调控内脏疼痛行为。

总之，他们的研究结果表明，谷氨酸能VTA神经元中NR2A的上调在内脏疼痛中起着关键作用。这些发现为进一步理解慢性内脏痛的神经回路和分子靶点提供了基础，并可能为慢性内脏痛的靶向治疗铺平道路。

附：英文原文

Title: Upregulation of NR2A in Glutamatergic VTA Neurons Contributes to Chronic Visceral Pain in Male Mice

Author: Li, Meng-Ge, Qu, Shu-Ting, Yu, Yang, Xu, Zhenhua, Zhang, Fu-Chao, Li, Yong-Chang, Gao, Rong, Xu, Guang-Yin

Issue&Volume: 2025-04-28

Abstract: Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca2+ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.

DOI: 10.1007/s12264-025-01402-7

Source: https://link.springer.com/article/10.1007/s12264-025-01402-7