Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

中文翻译：

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GABA能神经元对慢性炎症性疼痛大鼠模型前扣带皮层的抗焦虑作用

慢性疼痛容易导致伴随的情绪障碍，而前扣带皮层 (ACC) 锥体神经元 (PN) 的兴奋性与慢性疼痛相关的焦虑有关。然而，PNs 调节疼痛相关焦虑的机制仍然未知。GABAergic 系统在调节神经元活动中起重要作用。在本文中，我们旨在研究 GABA 能系统如何参与调节 ACC PN 的兴奋性，从而影响慢性炎症性疼痛相关的焦虑。CFA 诱导的慢性炎症性疼痛大鼠模型表现出焦虑样行为，增加 ACC PN 的兴奋性，减少抑制性突触前传递；然而，GAD65/67 的数量没有改变。有趣的是，ACC 内注射 GABAAR 激动剂蝇蕈醇可缓解焦虑样行为，但对慢性炎症性疼痛没有影响。ACC 内注射 GABAAR 拮抗剂印防己毒素可引起焦虑样行为，但对正常大鼠的疼痛没有影响。值得注意的是，ACC 中 GABA 能神经元的化学遗传学激活减轻了慢性炎症性疼痛和疼痛引起的焦虑样行为，增强了抑制性突触前传递，并降低了 ACC PN 的兴奋性。ACC 中 GABA 能神经元的化学遗传学抑制导致疼痛诱导的焦虑样行为，抑制性突触前传递减少，并增强 ACC PN 的兴奋性，但对正常大鼠的疼痛没有影响。我们证明 GABA 能系统介导 ACC 抑制性突触前传递的减少，