The projections from the anterior cingulate cortex to the nucleus accumbens and ventral tegmental area contribute to neuropathic pain-evoked aversion in rats
The projections from the anterior cingulate cortex to the nucleus accumbens and ventral tegmental area contribute to neuropathic pain-evoked aversion in rats
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从前扣带皮层到伏隔核和腹侧被盖区的投射导致大鼠神经性疼痛诱发的厌恶
DOI：
10.1016/j.nbd.2020.104862
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发表时间：
2020-07-01
影响因子：
6.1
通讯作者：
Ruan, Huai-Zhen
中科院分区：
文献类型：
--
作者：
Gao, Shi-Hao;Shen, Lin-Lin;Ruan, Huai-Zhen
虽然前扣带皮层（ACC）在神经病理性疼痛相关的厌恶中起着重要作用，但其机制尚未得到充分研究。中脑边缘多巴胺系统编码奖赏和厌恶，并参与慢性疼痛的加重。因此，我们研究了ACC是否通过控制中脑边缘多巴胺系统来调节对神经性疼痛的厌恶，在大鼠坐骨神经慢性压迫性损伤（CCI）模型中。利用顺行和逆行追踪，我们证实了一个亚组的ACC神经元投射到中脑边缘多巴胺系统的两个关键节点--中脑背盖核（NAc）和腹侧被盖区（VTA）。结合幼年大鼠CCI后7天的电生理结果，我们发现CCI后NAc/VTA投射神经元呈高兴奋性。化学发生抑制这些预测诱导条件性位置偏爱在年轻的成年大鼠CCI后10-14天，不调制诱发痛阈，而这些预测在假手术大鼠的激活模仿厌恶行为。此外，ACC投射的功能可能是由NAc D2型中棘神经元和VTA GABA能神经元介导的。综上所述，我们的研究结果表明，从ACC到NAc和VTA的投射介导了神经病理性疼痛相关的厌恶行为。
Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10-14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.