Institute of Translational Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; Department of Anesthesiology of East Hospital, Tongji University School of Medicine, Shanghai, China.
Institute of Translational Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China.
J Invest Dermatol. 2018 Aug;138(8):1843-1850. doi: 10.1016/j.jid.2018.02.019. Epub 2018 Feb 24.
Transient extracellular signal-regulated kinase (ERK) activation in the spinal cord triggers histamine-induced acute itch. However, whether persistent ERK activation plays an important role in chronic itch development remains unclear. This study investigated the role of spinal ERK activation in chronic itch. The results showed that repetitive DNFB painting on the nape of mice evoked not only initial scratching but also sustained, spontaneous scratching. In addition, DNFB induced itching rather than nociception, as demonstrated using a cheek model. Furthermore, ERK was persistently activated in the spinal cord of DNFB-treated mice, and the intrathecal inhibition of phosphorylation of ERK suppressed both spontaneous itching and ERK activation. ERK activation was observed in neurons but not in glia cells during chronic itch development. Finally, DNFB-induced spontaneous itching behavior and ERK activation were largely inhibited by the histamine H4 receptor antagonist JNJ7777120 but not by the H1 receptor antagonist chlorpheniramine. Our results indicate that persistent ERK activation via the histamine H4 receptor in spinal neurons underlies DNFB-induced chronic itch.
脊髓中瞬时细胞外信号调节激酶 (ERK) 的激活引发组胺诱导的急性瘙痒。然而，持续的 ERK 激活是否在慢性瘙痒的发展中起重要作用仍不清楚。本研究探讨了脊髓 ERK 激活在慢性瘙痒中的作用。结果表明，在小鼠颈背部反复涂抹二硝基氟苯 (DNFB) 不仅会引起初始搔抓，还会引起持续的自发性搔抓。此外，DNFB 引起的是瘙痒而不是痛觉，这一点可以通过颊模型得到证明。此外，DNFB 处理的小鼠脊髓中 ERK 持续激活，鞘内抑制 ERK 的磷酸化可抑制自发性瘙痒和 ERK 激活。在慢性瘙痒发展过程中，ERK 激活仅发生在神经元中，而不是神经胶质细胞中。最后，组胺 H4 受体拮抗剂 JNJ7777120 可显著抑制 DNFB 诱导的自发性瘙痒行为和 ERK 激活，但组胺 H1 受体拮抗剂氯苯那敏则无此作用。我们的结果表明，DNFB 诱导的慢性瘙痒是由脊髓神经元中通过组胺 H4 受体介导的持续 ERK 激活所引起的。
