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刺激伏隔核核心中的 GABA 能神经元改变眶下神经损伤大鼠模型中的三叉神经病理性疼痛反应。

Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury.

机构信息

Department of Medical Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, Korea.

ISCRM, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.

出版信息

Int J Mol Sci. 2021 Aug 5;22(16):8421. doi: 10.3390/ijms22168421.

Abstract

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

摘要

伏隔核核(NAcc)是大脑奖励回路的重要组成部分,但研究表明它也参与了疼痛回路。然而,其对三叉神经痛(TN)的影响及其潜在机制尚未完全阐明。因此,本研究旨在探讨光遗传刺激 NAcc 中 GABA 能神经元对 TN 动物模型的影响。动物被分为 TN、假手术和对照组。TN 通过眶下神经缩窄产生,光遗传病毒注入 NAcc。从丘脑腹后内侧核进行体内细胞外记录。评估刺激“ON”和“OFF”条件下行为反应的变化。在 TN 和假手术动物的 NAcc 中进行体内微透析。在光遗传刺激期间,电生理记录显示 TN 动物的紧张性和爆发性放电活动均减少,并且观察到行为反应明显改善。微透析与液相色谱/串联质谱分析相结合,揭示了 NAcc 中 GABA、谷氨酸、乙酰胆碱、多巴胺和瓜氨酸的细胞外浓度水平在光刺激下发生显著变化。总之,我们的结果表明,NAcc 刺激可能调节 TN 动物模型中三叉神经痛信号的传递。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5089/8395143/b6710f7a7c99/ijms-22-08421-g001.jpg

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