Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway

Background/Aims: Irritable bowel syndrome (IBS), defined as recurrent abdominal pain and changes in bowel habits, seriously affects quality of life and ability to work. Ghrelin is a brain-gut hormone, which has been reported to show antinociceptive effects in peripheral pain. We investigated the effect of ghrelin on visceral hypersensitivity and pain in a rat model of IBS. Methods: Maternal deprivation (MD) was used to provide a stress-induced model of IBS in Wistar rats. Colorectal distension (CRD) was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores. Rats that were confirmed to have visceral hypersensitivity after MD were injected with ghrelin (10 µg/kg) subcutaneously twice a week from weeks 7 to 8. [D-Lys3]-GHRP-6 (100 nmol/L) and naloxone (100 nmol/L) were administered subcutaneously to block growth hormone secretagogue receptor 1α (GHS-R1α) and opioid receptors, respectively. Expression of transient receptor potential vanilloid type 1 (TRPV1) and µ and κ opioid receptors (MOR and KOR) in colon, dorsal root ganglion (DRG) and cerebral cortex tissues were detected by western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical analyses and immunofluorescence. Results: Ghrelin treatment increased expression of opioid receptors and inhibited expression of TRPV1 in colon, dorsal root ganglion (DRG) and cerebral cortex. The antinociceptive effect of ghrelin in the rat model of IBS was partly blocked by both the ghrelin antagonist [D-Lys3]-GHRP-6 and the opioid receptor antagonist naloxone. Conclusion: The results indicate that ghrelin exerted an antinociceptive effect, which was mediated via TRPV1/opioid systems, in IBS-induced visceral hypersensitivity. Ghrelin might potentially be used as a new treatment for IBS.

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Tu1647 - The Role of Dectin-1 and Mast Cells in Visceral Hypersensitivity in Patients with Diarrhea-Predominant Irritable Bowel Syndrome

Gastroenterology ◽

10.1016/s0016-5085(18)33291-8 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-980-S-981

Author(s):

Chao Li ◽

Yan Chi

Keyword(s):

Irritable Bowel Syndrome ◽

Mast Cells ◽

Visceral Hypersensitivity ◽

Irritable Bowel

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Role of High-affinity Choline Transporter 1 in Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome

Journal of Neurogastroenterology and Motility ◽

10.5056/jnm18040 ◽

2018 ◽

Vol 24 (4) ◽

pp. 643-655 ◽

Cited By ~ 2

Author(s):

Meng-juan Lin ◽

Bao-ping Yu

Keyword(s):

Irritable Bowel Syndrome ◽

Rat Model ◽

Choline Transporter ◽

High Affinity ◽

Irritable Bowel ◽

High Affinity Choline Transporter

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P2X3 Receptor in Primary Afferent Neurons Mediates the Relief of Visceral Hypersensitivity by Electroacupuncture in an Irritable Bowel Syndrome Rat Model

Gastroenterology Research and Practice ◽

10.1155/2020/8186106 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Fang Zhang ◽

Zhe Ma ◽

Zhijun Weng ◽

Min Zhao ◽

Handan Zheng ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Rat Model ◽

Visceral Pain ◽

Visceral Hypersensitivity ◽

Receptor Protein ◽

Resting Membrane Potential ◽

Drg Neurons ◽

Expression Levels ◽

Behavioral Studies ◽

Irritable Bowel

Background. Electroacupuncture (EA) has been confirmed effectiveness in the treatment of irritable bowel syndrome (IBS), and P2X3 receptors in the peripheral and central neurons participate in the acupuncture-mediated relief of the visceral pain in IBS. Objective. To reveal the neurobiological mechanism that P2X3 receptor of colonic primary sensory neurons in the dorsal root ganglia of the lumbosacral segment is involved in the alleviation of visceral hypersensitivity by EA in an IBS rat model. Methods. The IBS chronic visceral pain rat model was established according to the method of Al-Chaer et al. EA at the bilateral He-Mu points, including ST25 and ST37, was conducted for intervention. The behavioral studies, histopathology of colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction assays were used to observe the role of P2X3 receptor in the colon and related DRG in relieving visceral hypersensitivity by EA. Results. EA significantly reduced the behavior scores of the IBS rats under different levels (20, 40, 60, 80 mmHg) of colorectal distention stimulation and downregulated the expression levels of P2X3 receptor protein and mRNA in colon and related DRG of the IBS rats. EA also regulated the electrical properties of the membranes, including the resting membrane potential, rheobase, and action potential of colon-associated DRG neurons in the IBS rats. Conclusion. EA can regulate the P2X3 receptor protein and mRNA expression levels in the colon and related DRG of IBS rats with visceral pain and then regulate the excitatory properties of DRG neurons.

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