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在改良的慢性缩窄性损伤诱导的小鼠神经性疼痛模型中,对感觉、情感、认知、生化和神经元改变进行特征描述。

Characterization of the sensory, affective, cognitive, biochemical, and neuronal alterations in a modified chronic constriction injury model of neuropathic pain in mice.

机构信息

Division of Pharmacology, Department of Experimental Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Ribeirão Preto (SP), Brazil.

出版信息

J Neurosci Res. 2020 Feb;98(2):338-352. doi: 10.1002/jnr.24501. Epub 2019 Aug 8.

Abstract

The chronic constriction injury (CCI) of the sciatic nerve is a nerve injury-based model of neuropathic pain (NP). Comorbidities of NP such as depression, anxiety, and cognitive deficits are associated with a functional reorganization of the medial prefrontal cortex (mPFC). Here, we have employed an adapted model of CCI by placing one single loose ligature around the sciatic nerve in mice for investigating the alterations in sensory, motor, affective, and cognitive behavior and in electrophysiological and biochemical properties in the prelimbic division (PrL) of the mPFC. Our adapted model of CCI induced mechanical allodynia, motor, and cognitive impairments and anxiety- and depression-like behavior. In the PrL division of mPFC was observed an increase in GABA and a decrease in d-aspartate levels. Moreover an increase in the activity of neurons responding to mechanical stimulation with an excitation, mPFC (+), and a decrease in those responding with an inhibition, mPFC (-), was found. Altogether these findings demonstrate that a single ligature around the sciatic nerve was able to induce sensory, affective, cognitive, biochemical, and functional alterations already observed in other neuropathic pain models and it may be an appropriate and easily reproducible model for studying neuropathic pain mechanisms and treatments.

摘要

慢性坐骨神经缩窄损伤(CCI)是一种基于神经损伤的神经性疼痛(NP)模型。NP 的合并症,如抑郁、焦虑和认知缺陷,与内侧前额叶皮层(mPFC)的功能重组有关。在这里,我们通过在小鼠的坐骨神经周围放置一个单松散结扎来采用改良的 CCI 模型,以研究感觉、运动、情感和认知行为以及 mPFC 的前扣带回(PrL)的电生理和生化特性的变化。我们改良的 CCI 模型诱导了机械性痛觉过敏、运动和认知障碍以及焦虑和抑郁样行为。在 mPFC 的 PrL 分部观察到 GABA 增加和 d-天冬氨酸水平降低。此外,还发现对机械刺激反应的神经元的活性增加,mPFC (+),以及对抑制反应的神经元减少,mPFC (-)。总之,这些发现表明,坐骨神经周围的单结扎能够诱导已经在其他神经性疼痛模型中观察到的感觉、情感、认知、生化和功能改变,它可能是研究神经性疼痛机制和治疗的一种合适且易于复制的模型。

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