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MrgprA3 shows sensitization to chloroquine in an acetone–ether–water mice model

Shi, Haoa,b,*; Yu, Guanga,b,*; Geng, Xiaoa,b; Gu, Leyinga,b; Yang, Niuniua,b; Wang, Changminga,b; Zhu, Chana,b; Yang, Yana,b; Yu, Leia,b; Hu, Danyoua,b; Yuan, Xiaolina,b; Lan, Leic; Wu, Guanyid; Tang, Zongxianga,b

doi: 10.1097/WNR.0000000000000877
Cellular, Molecular Anddevelopmental Neuroscience

Chronic itch, a distressing symptom of many cutaneous and systemic diseases, significantly impairs quality of life. However, its underlying molecular mechanism is still unclear. Mas-related G protein-coupled receptor A3 (MrgprA3) is considered an itch-specific receptor. MrgprA3+ neurons are identified as a class of itch-specific neurons, but the role of MrgprA3 in chronic itch remains elusive. An acetone–ether–water (AEW) model as a histamine-independent itch model is often used in the study of chronic pruritus. In this study, behavioral tests, immunostaining, cell culture, calcium imaging, and other experiments were carried out to examine the expression of MrgprA3. The results showed that the scratching bouts induced by chloroquine increased significantly under the AEW condition; the density of MrgprA3+ sensory fibers in the AEW-treated skin area and the number of MrgprA3+ neurons in dorsal root ganglia from the AEW model mice also increased significantly. Further analysis showed that the MrgprA3 in mRNA level was also increased after AEW treatment. These results indicated that MrgprA3 played a crucial role in chronic pruritus in the AEW model.

aDepartment of Physiology, School of Medicine and Life Sciences

bKey Laboratory of Prevention and Treatment of Chinese Medicine in Neurological Disease, Nanjing University of Chinese Medicine

cDepartment of Biochemistry, College of Life Sciences, Nanjing Normal University, Nanjing

dDepartment of Physiology, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, China

* Hao Shi and Guang Yu contributed equally to the writing of this article.

Correspondence to Zongxiang Tang, PhD, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, Jiangsu, China Tel/fax: + 86 258 581 1802; e-mail: zongxiangtang@njutcm.edu.cn

Received June 21, 2017

Accepted July 17, 2017

© 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins