Yiwen Zhang1  · Jiaqi Li1  · You Wu1  · Jialin Si2  · Yuanyuan Zhu1  · Meng Nian2  · Chen Chen1  · Ningcan Ma1  · Xiaolin Zhang1  · Yaoyuan Zhang1  · Yiting Lin1,3  · Ling Liu3  · Yang Bai4  · Shengxi Wu1  · Jing Huang1

1 Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China 

2 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China 

3 Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China 

4 Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110015, China

Abstract

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.

Keywords

Anterior cingulate cortex; Vasoactive intestinal peptide; Itch; Pain

[SpringerLink]