The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats
The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats
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DOI：
10.1089/neu.2017.5381
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发表时间：
2018-04-20
影响因子：
4.2
通讯作者：
Gwak, Young S.
中科院分区：
文献类型：
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作者：
Ko, Moon Yi;Jang, Eun Young;Gwak, Young S.
脊髓损伤(SCI)常导致慢性神经病理性疼痛(CNP)。然而，对CNP调制中脑神经回路的了解尚不清楚。本研究观察了大鼠腹侧被盖区(VTA)GABA能和多巴胺能神经元活动随CNP衰减的变化。采用T10夹闭法(35g，1min)复制大鼠脊髓损伤模型，分别观察大鼠神经病理性疼痛行为、VTAγ-氨基丁酸(GABA)/多巴胺神经元细胞外单细胞记录、细胞外GABA水平、谷氨酸脱羧酶(GAD)和囊泡GABA转运体(VGATs)的变化。结果显示，CNP组细胞外GABA水平(50.5+/-18.9 nM)显著高于假手术对照组(10.2+/-1.7 nM)。此外，与假手术对照组相比，脊髓损伤组GAD(65/67)、c-Fos和VGAT表达显著增加。在神经病理性疼痛行为方面，超声发声(USVs)测量的自发性疼痛和爪部收缩阈值测量的诱发性疼痛显示出显著的变化，而静脉注射(Iv)则逆转了这一变化。注射吗啡(0.5-5.0 mg/kg)。在体内电生理方面，脊髓损伤组VTA GABA能神经元活动(13.6+/-1.7个峰/秒)和多巴胺能神经元活动(2.4+/-0.8个峰/秒)分别比假手术对照组增加和降低。这些神经元活动可被静脉注射逆转。注射吗啡。本研究提示，GABA能神经元活动的慢性增加抑制了VTA内的多巴胺能神经元的活动，这是脊髓损伤后CNP减弱的负性情绪和动机的原因之一。
Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI was established by T10 clip compression injury (35 g, 1 min) in rats, and neuropathic pain behaviors, in vivo extracellular single-cell recording of putative VTA gamma-aminobutyric acid (GABA)/dopamine neurons, extracellular GABA level, glutamic acid decarboxylase (GAD), and vesicular GABA transporters (VGATs) were measured in the VTA, respectively. The results revealed that extracellular GABA level was significantly increased in the CNP group (50.5 +/- 18.9 nM) compared to the sham control group (10.2 +/- 1.7 nM). In addition, expression of GAD(65/67), c-Fos, and VGAT exhibited significant increases in the SCI groups compared to the sham control group. With regard to neuropathic pain behaviors, spontaneous pain measured by ultrasound vocalizations (USVs) and evoked pain measured by paw withdrawal thresholds showed significant alteration, which was reversed by intravenous (i.v.) administration of morphine (0.5-5.0 mg/kg). With regard to in vivo electrophysiology, VTA putative GABAergic neuronal activity (13.6 +/- 1.7 spikes/sec) and putative dopaminergic neuronal activity (2.4 +/- 0.8 spikes/sec) were increased and decreased, respectively, in the SCI group compared to the sham control group. These neuronal activities were reversed by i.v. administration of morphine. The present study suggests that chronic increase of GABAergic neuronal activity suppresses dopaminergic neuronal activity in the VTA and is responsible for negative emotion and motivation for attenuation of SCI-induced CNP.