Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain–gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBS-like syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.