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.

慢性内脏超敏反应 (CVH) 是肠易激综合征 (IBS) 和其他内脏疼痛疾病患者的主要病理生理特征。然而，关于它对中央核的调节知之甚少。在这项研究中，我们研究了下丘脑室旁核 (PVN) 微量注射谷氨酸盐对大鼠 CVH 的保护作用及其可能的调节机制。通过疼痛阈值、腹部撤退反射 (AWR) 评分和腹部外斜肌肌电图 (EMG) 幅度评估内脏敏感性。使用免疫组织化学、生化分析和蛋白质印迹评估结肠直肠粘膜的病理变化。结果表明，将不同剂量的谷氨酸显微注射到 PVN 中以剂量依赖性方式降低内脏敏感性。这种作用可以在 PVN 或孤束核 (NTS) 化学消融或用精氨酸加压素 (AVP)-V 预处理后逆转₁受体拮抗剂（[Deamino-pen ¹ ,val ⁴ ,D-Arg ⁸ ]-加压素）DPVDAV 进入 NTS。将谷氨酸盐显微注射到 PVN 后，迷走神经放电频率显着降低。此外，结直肠黏膜的氧化、增殖和凋亡与 CVH 调节有关。这些发现表明PVN和NTS参与了CVH的调控过程并对CVH发挥了保护作用，为CVH研究提供了新的思路和治疗靶点。