A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity.
A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity.
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背内侧前额叶皮质中的伤害性神经元是慢性疼痛的基础。
DOI：
10.1016/j.celrep.2022.111833
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发表时间：
2022-12
期刊：
影响因子：
8.8
通讯作者：
X. Qi;Kun Cui;Yu Zhang;Linshu Wang;Jifu Tong;Weiqi Sun;Shan Shao;Jiaxin Wang;Cheng Wang;Xiaoyan Sun;Liming Xiao;Ke Xi;Shuang Cui;Fengyu Liu;Longyu Ma;Jie Zheng;Ming Yi;You Wan
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文献类型：
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作者：
X. Qi;Kun Cui;Yu Zhang;Linshu Wang;Jifu Tong;Weiqi Sun;Shan Shao;Jiaxin Wang;Cheng Wang;Xiaoyan Sun;Liming Xiao;Ke Xi;Shuang Cui;Fengyu Liu;Longyu Ma;Jie Zheng;Ming Yi;You Wan
慢性疼痛包括躯体感觉和情感方面的不愉快体验，并伴有前额叶皮质(PFC)神经可塑性改变。然而，是否特定的PFC神经元集合是慢性疼痛的基础仍然难以捉摸。在这里，我们确定了背内侧前额叶皮质(DmPFC)中的一个伤害性神经元集合，它对伤害性刺激表现出显著的反应。我们观察到，这个集合显示出明显的分子特征，并与疼痛相关区域紧密联系，包括杏仁基底外侧核(BLA)和臂旁外侧核(LPB)。这种伤害性神经元的长期化学激活，但不是随机转染的dmPFC神经元的子集，会在正常小鼠中诱导慢性疼痛行为。相比之下，沉默伤害性dmPFC神经元可以缓解慢性炎症性疼痛小鼠的疼痛过敏和焦虑。这些结果表明，在处理伤害性信息和调节疼痛慢性化方面存在特定的dmPFC神经元群。
Pain chronicity involves unpleasant experience in both somatosensory and affective aspects, accompanied with the prefrontal cortex (PFC) neuroplastic alterations. However, whether specific PFC neuronal ensembles underlie pain chronicity remains elusive. Here we identify a nociceptive neuronal ensemble in the dorsomedial prefrontal cortex (dmPFC), which shows prominent reactivity to nociceptive stimuli. We observed that this ensemble shows distinct molecular characteristics and is densely connected to pain-related regions including basolateral amygdala (BLA) and lateral parabrachial nuclei (LPB). Prolonged chemogenetic activation of this nociceptive neuronal ensemble, but not a randomly transfected subset of dmPFC neurons, induces chronic pain-like behaviors in normal mice. By contrast, silencing the nociceptive dmPFC neurons relieves both pain hypersensitivity and anxiety in mice with chronic inflammatory pain. These results suggest the presence of specific dmPFC neuronal ensembles in processing nociceptive information and regulating pain chronicity.