Tail clamping induces anxiety-like behaviors and visceral hypersensitivity in rat models of non-erosive reflux disease
Abstract
BACKGROUND Non-erosive reflux disease (NERD), the main gastroesophageal reflux subtype, features reflux symptoms without mucosal damage. Anxiety links to visceral hypersensitivity in NERD, yet mechanisms and animal models are unclear. AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone (CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury. METHODS Sprague-Dawley (SD) and Wistar rats were grouped into sham, model, and modified groups (n = 10 each). The treatments for the modified groups were as follows: SD rats received ovalbumin/aluminum hydroxide suspension + acid perfusion ± tail clamping (40 minutes/day for 7 days), while Wistar rats received fructose water + tail clamping. Esophageal pathology, visceral sensitivity, and behavior were assessed. Serum CRH, calcitonin gene-related peptide (CGRP), 5-hydroxytryptamine (5-HT), and mast cell tryptase (MCT) and central amygdala (CeA) CRH mRNA were measured via ELISA and qRT-PCR. RESULTS Tail clamping induced anxiety, worsening visceral hypersensitivity (lower abdominal withdrawal reflex thresholds, P < 0.05) and esophageal injury (dilated intercellular spaces and mitochondrial edema). Both models showed raised serum CRH, CGRP, 5-HT, and MCT (P < 0.01) and CeA CRH mRNA expression (P < 0.01). Behavioral tests confirmed anxiety-like phenotypes. NERD-anxiety rats showed clinical-like symptom severity without erosion.…
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