Abstract
Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.
Highlights
Irritable bowel syndrome (IBS) is a common gut disorder with altered bowel habits, abdominal bloating, and discomfort [1]
abdominal withdrawal reflex (AWR) score and threshold pressure to Colorectal distension (CRD) reflected the responses of visceral hypersensitivity
After 10 days of water avoidance stress (WAS), the mean threshold of CRD was significantly lower (P = 0 035, Figure 1(a)), and the AWR score was significantly higher at the distension pressures of 40, 60, and 80 mmHg compared to the sham stress rats (P = 0 011, 0.001, and 0.049, resp., Figure 1(b))
Summary
Irritable bowel syndrome (IBS) is a common gut disorder with altered bowel habits, abdominal bloating, and discomfort [1]. It is reported that cholinergic system involves in the development of visceral hypersensitivity [8, 9]. Our previous study has showed that CHT1 is Gastroenterology Research and Practice increased in the model of pancreatitis-induced pain, and CHT1 inhibitor can enhance the behavioral response to abdominal mechanical stimulation in rats [12]. The involvement of CHT1 in the noninflammatory visceral hypersensitivity induced by chronic stress remains unknown. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats.
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