The anterior cingulate cortex (ACC) plays a crucial role in the perception of pain. It is consistently activated by noxious stimuli and its hyperactivity in chronic pain indicates plasticity in the local neuronal network. However, the way persistent pain effects and modifies different neuronal cell types in the ACC and how this contributes to sensory sensitization is not completely understood. This study confirms the existence of 2 primary subtypes of pyramidal neurons in layer 5 of the rostral, agranular ACC, which we could classify as intratelencephalic (IT) and cortico-subcortical (SC) projecting neurons, similar to other cortical brain areas. Through retrograde labeling, whole-cell patch-clamp recording, and morphological analysis, we thoroughly characterized their different electrophysiological and morphological properties. When examining the effects of peripheral inflammatory pain on these neuronal subtypes, we observed time-dependent plastic changes in excitability. During the acute phase, both subtypes exhibited reduced excitability, which normalized to pre-inflammatory levels after day 7. Daily conditioning with nociceptive stimuli during this period induced an increase in excitability specifically in SC neurons, which was correlated with a decrease in mechanical sensitization. Subsequent inhibition of the activity of SC neurons projecting to the periaqueductal gray with in vivo chemogenetics, resulted in reinstatement of the hypersensitivity. Accordingly, it was sufficient to enhance the excitability of these neurons chemogenetically in the inflammatory pain condition to induce hypoalgesia. These findings suggest a cell type-specific effect on the descending control of nociception and a cellular mechanism for pain-induced analgesia. Furthermore, increased excitability in this neuronal population is hypoalgesic rather than hyperalgesic.

中文翻译：

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有助于疼痛诱导镇痛的细胞机制。


前扣带皮层（ACC）在疼痛感知中起着至关重要的作用。它持续被有害刺激激活，其在慢性疼痛中的过度活跃表明局部神经元网络的可塑性。然而，持续性疼痛如何影响和改变 ACC 中不同类型的神经元细胞以及它如何促进感觉敏化尚不完全清楚。这项研究证实了头侧无颗粒 ACC 第 5 层存在两种主要的锥体神经元亚型，我们可以将其分类为端脑内 (IT) 和皮质-皮质下 (SC) 投射神经元，与其他皮质脑区域类似。通过逆行标记、全细胞膜片钳记录和形态学分析，我们彻底表征了它们不同的电生理和形态学特性。当检查外周炎性疼痛对这些神经元亚型的影响时，我们观察到兴奋性随时间变化的可塑性变化。在急性期，两种亚型都表现出兴奋性降低，第 7 天后恢复到炎症前水平。在此期间每天接受伤害性刺激会导致 SC 神经元的兴奋性增加，特别是 SC 神经元的兴奋性增加，这与机械敏化的减少相关。随后用体内化学遗传学抑制投射到导水管周围灰质的 SC 神经元的活性，导致超敏反应的恢复。因此，在炎性疼痛条件下，足以通过化学遗传学增强这些神经元的兴奋性以诱导痛觉减退。这些发现表明细胞类型特异性对伤害感受的下降控制产生影响，以及疼痛诱导镇痛的细胞机制。 此外，该神经元群的兴奋性增加是痛觉减退而非痛觉过敏。