Protective effect of microinjection of glutamate into hypothalamus paraventricular nucleus on chronic visceral hypersensitivity in rats

• Published in: Brain research 2020-11, Vol.1747, p.147048-147048, Article 147048
• Main Authors: Su, Zhen, Miao, Bei, Xu, Man-qiu, Yang, Min-jie, Fei, Su-juan, Zhang, Jian-fu
• Format: Article
• Language: English
• Subjects: Arginine vasopressin; Glutamate; Nucleus tractus solitarius; Paraventricular nucleus; Visceral hypersensitivity
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2020.147048

•We found that glutamate stimulation of PVN reduced visceral sensitivity in the CVH rats.•We clarified that chemical ablation of PVN or NTS reversed the effect of PVN on CVH.•The microinjection of AVP-V1 receptor antagonist DPVDAV into NTS promoted CVH.•The vagal nerve is participated in the CVH process.•We first reported that PVN and NTS are involved in the regulation of CVH. Chronic visceral hypersensitivity (CVH) is a major pathophysiological feature of patients experiencing in irritable bowel syndrome (IBS) and other disorders with visceral pain. However, little is known about its regulation of the central nucleus. In this research, we investigated the protective effect of microinjection of glutamate into hypothalamus paraventricular nucleus (PVN) on CVH and its possible regulatory mechanism in rats. Visceral sensitivity was assessed by pain threshold, abdominal withdrawal reflex (AWR) score, and the abdominal external oblique muscle electromyography (EMG) amplitude. Pathological changes in colorectal mucosa were assessed using immunohistochemical, biochemical analysis and Western blot. Results showed that microinjection of different doses of glutamate into PVN reduced the visceral sensitivity in a dose-dependent manner. This effect can be reversed after chemical ablation of PVN or nucleus tractus solitarius (NTS) or pretreatment with the arginine vasopressin (AVP)-V1 receptor antagonist ([Deamino-pen1,val4,D-Arg8]-vasopressin) DPVDAV into NTS. The vagus discharge frequency was significantly reduced after the glutamate microinjection into PVN. Additionally, oxidation, proliferation and apoptosis in colorectal mucosa were related to the CVH regulations. These findings suggested that PVN and NTS are involved in the regulatory process of CVH and exert the protective effect on CVH, providing new ideas and therapeutic targets for CVH research.