Intractable scratching is the characteristic of chronic itch, which represents a great challenge in clinical practice. However, the mechanism underlying chronic itch development is largely unknown. In the present study, we investigated the role of NMDA receptor in acute itch and in development of chronic itch. A mouse model was developed by painting DNFB to induce allergic contact dermatitis (ACD). We found that the expression of pNR1, which is a subunit of NMDA receptor, was significantly increased in the dorsal root ganglion in the DNFB model. The DNFB-evoked spontaneous scratching was blocked by the NMDA antagonist D-AP-5, the calcium-calmodulin-dependent protein kinase (CaMK) inhibitor KN-93, a CaMKIIα siRNA and the PKC inhibitor LY317615. Moreover, activation of PKC did not reverse the CaMKIIα knockdown-induced decrease in scratching, suggesting that PKC functions upstream of CaMKIIα. Thus, our study indicates that modulation of NR1 receptor by CaMKIIα plays an important role in the development of chronic itch.

中文翻译：

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CaMKIIα 对 NR1 受体的调节在小鼠慢性瘙痒的发展中起重要作用。

顽固性抓挠是慢性瘙痒的特征，这对临床实践提出了巨大的挑战。然而，慢性瘙痒发展的机制在很大程度上是未知的。在本研究中，我们研究了 NMDA 受体在急性瘙痒和慢性瘙痒发展中的作用。通过涂抹 DNFB 来诱导过敏性接触性皮炎 (ACD) 开发了一种小鼠模型。我们发现，在 DNFB 模型的背根神经节中，作为 NMDA 受体亚基的 pNR1 的表达显着增加。DNFB 诱发的自发性抓挠被 NMDA 拮抗剂 D-AP-5、钙钙调蛋白依赖性蛋白激酶 (CaMK) 抑制剂 KN-93、CaMKIIα siRNA 和 PKC 抑制剂 LY317615 阻断。此外，PKC 的激活并没有逆转 CaMKIIα 敲低诱导的抓挠减少，表明 PKC 在 CaMKIIα 上游起作用。因此，我们的研究表明，CaMKIIα 对 NR1 受体的调节在慢性瘙痒的发展中起着重要作用。