Diabetic neuropathic pain (DNP) is a common chronic complication of diabetes mellitus and a clinically common form of neuropathic pain (NP). The thalamus is an important center for the conduction and modulation of nociceptive signals. The paraventricular thalamic nucleus (PVT) is an important midline nucleus of the thalamus involved in sensory processing, but the specific role of PVT astrocytes and GABAergic neurons in DNP remains unclear. Here, we examined the activity of PVT astrocytes and neurons at various time points during the development of DNP by fluorescence immunohistochemistry and found that the activity of PVT astrocytes was significantly increased while that of PVT neurons was significantly decreased 14 days after streptozotocin (STZ) injection in male rats. The inhibition of PVT astrocytes by chemogenetic manipulation relieved mechanical allodynia in male DNP model rats, whereas the activation of PVT astrocytes induced mechanical allodynia in normal male rats. Interestingly, chemogenetic activation of GABAergic neurons in the PVT alleviated mechanical allodynia in male DNP model rats, whereas chemogenetic inhibition of GABAergic neurons in the PVT induced mechanical allodynia in normal male rats. These data demonstrate the distinct roles of PVT astrocytes and GABAergic neurons in modulating DNP, revealing the mechanism of DNP pathogenesis and the role of the PVT in pain modulation.Significance Statement Some studies have focused on the role of paraventricular thalamic nucleus (PVT) glutamatergic neurons in neuropathic pain (NP) and anxiety. However, the role of PVT astrocytes and GABAergic neurons in diabetic neuropathic pain (DNP) has not been studied. We used chemogenetic techniques to bidirectionally regulate the activity of PVT astrocytes or GABAergic neurons and found that PVT astrocyte activation promotes NP, while PVT GABAergic neuron activation may mediate antinociceptive effects. These findings clarify the critical roles of PVT astrocytes and GABAergic neurons in modulating DNP, providing insight for the development of new strategies for the prevention and treatment of DNP and revealing the mechanism of DNP pathogenesis and the role of the PVT in pain modulation.

中文翻译：

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星形胶质细胞和 GABA 能神经元在室旁丘脑核中调节糖尿病神经性疼痛中的不同作用。


糖尿病神经性疼痛 （DNP） 是糖尿病的常见慢性并发症，也是临床上常见的神经性疼痛 （NP） 形式。丘脑是传导和调节伤害性信号的重要中心。室旁丘脑核 （PVT） 是丘脑的重要中线核，参与感觉处理，但 PVT 星形胶质细胞和 GABA 能神经元在 DNP 中的具体作用尚不清楚。在这里，我们通过荧光免疫组化检测了 DNP 发展过程中不同时间点 PVT 星形胶质细胞和神经元的活性，发现雄性大鼠注射链脲佐菌素 （STZ） 后 14 天，PVT 星形胶质细胞的活性显着增加，而 PVT 神经元的活性显着降低。通过化学遗传学操作抑制 PVT 星形胶质细胞缓解了雄性 DNP 模型大鼠的机械异常性疼痛，而 PVT 星形胶质细胞的激活诱导了正常雄性大鼠的机械异常性疼痛。有趣的是，PVT 中 GABA 能神经元的化学遗传学激活减轻了雄性 DNP 模型大鼠的机械异常性疼痛，而 PVT 中 GABA 能神经元的化学遗传学抑制诱导了正常雄性大鼠的机械异常性疼痛。这些数据证明了 PVT 星形胶质细胞和 GABA 能神经元在调节 DNP 中的不同作用，揭示了 DNP 发病机制和 PVT 在疼痛调节中的作用。意义声明 一些研究集中在室旁丘脑核 （PVT） 谷氨酸能神经元在神经性疼痛 （NP） 和焦虑中的作用。然而，尚未研究 PVT 星形胶质细胞和 GABA 能神经元在糖尿病神经性疼痛 （DNP） 中的作用。 我们使用化学遗传学技术双向调节 PVT 星形胶质细胞或 GABA 能神经元的活性，发现 PVT 星形胶质细胞活化促进 NP，而 PVT GABA 能神经元激活可能介导抗伤害性作用。这些发现阐明了 PVT 星形胶质细胞和 GABA 能神经元在调节 DNP 中的关键作用，为预防和治疗 DNP 的新策略的开发提供了见解，并揭示了 DNP 发病机制和 PVT 在疼痛调节中的作用。