Role of nucleus accumbens in neuropathic pain: linked multi-scale evidence in the rat transitioning to neuropathic pain.
Role of nucleus accumbens in neuropathic pain: linked multi-scale evidence in the rat transitioning to neuropathic pain.
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DOI：
10.1016/j.pain.2014.02.019
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发表时间：
2014-06
期刊：
影响因子：
7.4
通讯作者：
Apkarian AV
中科院分区：
文献类型：
--
作者：
Chang PC;Pollema-Mays SL;Centeno MV;Procissi D;Contini M;Baria AT;Martina M;Apkarian AV
尽管最近的证据表明，神经核（NAc）作为因果关系参与人类慢性疼痛的过渡，这种参与的潜在机制仍然完全未知。在这里，我们阐明NAc重组特性（纵向和横截面）的机制，在神经性疼痛（备用神经损伤，SNI）的动物模型。我们观察到以下相互关联的变化：1）在静息态fMRI中，NAc与背侧纹状体和皮质的功能连接在28天后减少（2）SNI后28天，SNI对侧NAc多巴胺1A、2和κ阿片受体基因表达下降; 3）在SNI（但不是假手术）中，基因表达的协方差在第5天上调，并在第28天稳定到新的状态;和4）NAc功能连接与多巴胺受体基因表达和触觉异常性疼痛相关。此外，NAc活性的中断（通过利多卡因输注）可逆地减轻了SNI动物的神经性疼痛。总之，这些结果表明宏观（功能磁共振成像）和分子重组的NAc，并表明，NAc神经元的活动是必要的神经性疼痛样行为的充分表达。
Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury, SNI). We observed inter-related changes: 1) In resting-state fMRI, functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; 2) contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; 3) In SNI (but not sham) covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and 4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.