机构：[1]Department of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, China[2]Laboratory of Sensory Neurobiology, Department of Human Anatomy, Histology and Embryology, Tongji University School of Medicine, Shanghai, China[3]Department of Dermatology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Department of Pathology, Naval Medical Center, Naval Medical University, Shanghai, China
Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.
基金：
This work was supported by National Key R&D Program of China,
2021YFA1201400 (to L.Z.); National Natural Science Foundation of
China, No. 32271058 (to L.Z.); the Natural Science Foundation of
Shanghai, No. 21ZR1468600 (to L.Z.).
第一作者机构：[1]Department of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, China[2]Laboratory of Sensory Neurobiology, Department of Human Anatomy, Histology and Embryology, Tongji University School of Medicine, Shanghai, China
通讯作者：
通讯机构：[1]Department of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, China[2]Laboratory of Sensory Neurobiology, Department of Human Anatomy, Histology and Embryology, Tongji University School of Medicine, Shanghai, China[4]Department of Pathology, Naval Medical Center, Naval Medical University, Shanghai, China[*1]Tongji University School of Medicine, Shanghai, 200000, China[*2]Department of Pathology, Naval Medical Center, Naval Medical University, Shanghai 200052, China
推荐引用方式(GB/T 7714)：
Wang Ting-Ting,Li Zi-Yang,Hu Dan-Dan,et al.Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice[J].EXPERIMENTAL DERMATOLOGY.2024,33(7):doi:10.1111/exd.15128.
