PRG-1 Relieves Neonatal Stimuli-Induced Hyperalgesia and Anxiety via Stage-Specific Synapse Remodeling

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-08-18 DOI:10.1111/cns.70560

Wenyu Zhang, Yan Li, Guangda Liang, Qingmei Li, Zhouyi Song, Song Cao, Zhi Xiao, Xingfeng Liu

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引用次数: 0

Abstract

Objective

Neonatal repetitive noxious stimuli (RNS), to mimic early-life repetitive pain exposure, induce persistent hyperalgesia, anxiety-like behaviors and postoperative pain sensitization that endure into adulthood. These long-term neurobehavioral abnormalities are associated with impaired cognitive, emotional, and psychosocial functions.

Method

We established a neonatal RNS rat model through repetitive needle pricks to all four limbs of neonatal rats and investigated the effects of hippocampal PRG-1 and synaptic remodeling at different stages in RNS rat.

Results

Our study demonstrates that hippocampal PRG-1 dynamically modulates RNS-induced hyperalgesia and anxiety through stage-specific regulation of AMPAR GluR1/GluR2 and NMDAR GluN2A/GluN2B trafficking, which leads to synaptic remodeling via altered dendritic synaptic morphology and synaptic transmission efficacy.

Conclusion

Our findings suggest that PRG-1 relieves RNS-induced persistent hyperalgesia, anxiety, and pain-perception memory via synapse remodeling at different stages. Targeting PRG-1-mediated synaptic remodeling may provide a novel neuroprotective strategy for preventing chronic pain comorbidities with anxiety disorders following early-life pain exposure.

Abstract Image

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PRG-1通过阶段特异性突触重塑缓解新生儿刺激诱导的痛觉过敏和焦虑

目的：新生儿重复性有害刺激（RNS）模拟早期重复性疼痛暴露，诱导持续的痛觉过敏、焦虑样行为和术后疼痛致敏，并持续到成年期。这些长期的神经行为异常与认知、情感和社会心理功能受损有关。方法通过对新生大鼠四肢进行重复针刺，建立新生大鼠RNS模型，观察RNS大鼠不同阶段海马PRG-1及突触重构的影响。结果我们的研究表明，海马PRG-1通过对AMPAR GluR1/GluR2和NMDAR GluN2A/GluN2B转运的阶段特异性调控，动态调节rns诱导的痛觉过敏和焦虑，并通过改变树突突触形态和突触传递效率导致突触重塑。结论PRG-1可通过不同阶段的突触重构来缓解rns诱导的持续性痛觉过敏、焦虑和痛觉记忆。靶向prg -1介导的突触重塑可能为预防早期疼痛暴露后慢性疼痛伴焦虑障碍提供一种新的神经保护策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.