Adaptive alterations in the mesoaccumbal network after peripheral nerve injury.
Adaptive alterations in the mesoaccumbal network after peripheral nerve injury.
复制标题
周围神经损伤后中珠网络的适应性改变。
DOI：
10.1097/j.pain.0000000000002092
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发表时间：
2021-03-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
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作者：
延髓核（NAc）和腹侧被盖区（VTA）是控制慢性疼痛的脑回路中的关键枢纽。然而，这两个区域如何相互作用以形成慢性疼痛状态却知之甚少。我们的研究表明，在小鼠中，备用神经损伤（SNI）诱导的D2-受体的功能连接体的变化，在核心区域的NAC增强与边缘前皮质的连接，并削弱他们与基底外侧杏仁核的棘状投射神经元。这些变化，这是由于部分SNI诱导的抑制腹侧被盖区多巴胺能信号传导，是适应性的，因为模仿他们的化学发生减轻焦虑和社会退缩伴随损伤。相比之下，化学增强活动的腹侧被盖区多巴胺能神经元投射到内侧壳的NAc选择性抑制触觉异常性疼痛在SNI小鼠。这些结果表明，SNI诱导区域特异性改变VTA多巴胺能信号在NAc，以促进损伤后的环境再参与。然而，抵消性的自我平衡机制限制了这些适应性变化，可能导致慢性疼痛状态。
The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are critical hubs in the brain circuitry controlling chronic pain. Yet, how these 2 regions interact to shape the chronic pain state is poorly understood. Our studies show that in mice, spared nerve injury (SNI) induced alterations in the functional connectome of D2-receptor expressing spiny projection neurons in the core region of the NAc—enhancing connections with prelimbic cortex and weakening them with basolateral amygdala. These changes, which were attributable in part to SNI-induced suppression of VTA dopaminergic signaling, were adaptive because mimicking them chemogenetically alleviated the anxiety and social withdrawal accompanying injury. By contrast, chemogenetic enhancement of activity in VTA dopaminergic neurons projecting to the medial shell of the NAc selectively suppressed tactile allodynia in SNI mice. These results suggest that SNI induces regionally specific alterations in VTA dopaminergic signaling in the NAc to promote environmental reengagement after injury. However, countervailing, homeostatic mechanisms limit these adaptive changes, potentially leading to the chronic pain state.
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影响因子：
16.2
作者：
Baliki, Marwan N.;Geha, Paul Y.;Fields, Howard L.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
4.7
作者：
Lammel S;Lim BK;Malenka RC
通讯作者：
Malenka RC
影响因子：
4
作者：
Miller, Lisa Renee;Cano, Annmarie
通讯作者：
Cano, Annmarie
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
64.8
作者：
通讯作者：
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