Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state.
Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state.
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DOI：
10.2147/jpr.s170167
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发表时间：
2018
影响因子：
2.7
通讯作者：
Liu SJ
中科院分区：
文献类型：
--
作者：
Fu B;Wen SN;Wang B;Wang K;Zhang JY;Weng XC;Liu SJ
中脑被盖区（VTA）多巴胺系统在抑郁症中起重要作用，同时也参与疼痛体验。本研究通过观察疼痛相关抑郁症患者腹侧被盖区多巴胺能神经元放电和局部场电位的变化，探讨疼痛与抑郁症之间的内在联系。我们使用神经病理性疼痛模型[备用神经损伤（SNI）]诱导疼痛相关抑郁。采用狄克逊升降法检测机械超敏反应。采用旷场实验、蔗糖偏好实验、强迫游泳实验等行为学方法检测抑郁样行为。加巴喷丁（GBP）是一种可逆转疼痛相关抑郁的慢性镇痛药物。为了研究腹侧被盖区DA神经元放电和LFP的体内变化，使用多通道采集处理器系统。我们使用SNI诱导抑郁样行为。注射14天后，重复GBP治疗逆转了这些行为。对腹侧被盖区DA神经元和LFP放电特性的在体电生理分析表明，SNI增加DA神经元的放电频率，但不增加爆发放电活动。令人惊讶的是，慢性GBP逆转了DA神经元的放电率，减少了爆发放电活动。此外，SNI增加了δ和θ振荡的LFP功率，并降低了β振荡的LFP功率。GBP的重复给药显著抑制θ振荡。最重要的是，慢性GBP改变了这些特征，以逆转抑郁样行为。本研究证实腹侧被盖区DA能神经元的紧张性放电活动，而不是爆发性放电活动，是周围神经病诱发抑郁的关键因素。慢性GBP调节DA神经元的放电模式，减少VTA的θ振荡，以治疗疼痛相关的抑郁症。腹侧被盖区DA能神经元电生理特性的变化趋势和腹侧被盖区θ波振荡的变化趋势可能是科普疼痛相关的负性情绪障碍的一种尝试。
Ventral tegmental area (VTA) dopamine system plays an important role in depression and is also involved in pain experience. In this study, we investigated the VTA dopaminergic (DA) neuron firing and local field potential (LFP) in pain-related depression, and we try to explore the underlying relationship between pain and depression. We used neuropathic pain model [spare nerve injury (SNI)] to induce pain-related depression. The Dixon up–down method was used to test mechanical hypersensitivity. Behavioral changes like open field test, sucrose preference test, and forced swim test were used to test depression-like behaviors. Gabapentin (GBP) was used to explore the chronic analgesic treatment that could reverse pain-related depression. To investigate the in vivo variations of VTA DA neuron firing and LFP, multichannel acquisition processor system was used. We used SNI to induce depression-like behaviors. Repeated GBP treatment reversed these behaviors after 14 days of injection. An in vivo electrophysiological analysis of the firing characteristics of VTA DA neurons and LFP revealed that SNI increased the firing rate of DA neurons, but not the burst firing activity. Surprisingly, chronic GBP reversed the firing rate of DA neurons and reduced the burst firing activity. Moreover, SNI increased the LFP power in delta and theta oscillation and decreased it in beta oscillation. Repeated administration of GBP significantly suppressed theta oscillation. Above all, chronic GBP altered these characteristics to reverse depression-like behaviors. The present study confirmed that the tonic firing activity of VTA DA neurons, but not the burst firing activity, was the key factor in peripheral neuropathy–induced depression. Chronic GBP regulated the firing pattern of DA neurons and decreased theta oscillation in VTA to treat pain-related depression. This variation tendency of electrophysiological characteristics of VTA DA neurons and theta oscillation in VTA might represent an attempt to cope with pain-related negative mood disorder.