Abdominal Massage Reduces Visceral Hypersensitivity via Regulating GDNF and PI3K/AKT Signal Pathway in a Rat Model of Irritable Bowel Syndrome

Changes in gut motility and visceral hypersensitivity are two major features of irritable bowel syndrome (IBS). Current drug treatments are often poorly efficacious, with many side effects for patients with IBS. Complementary therapies, such as acupuncture or abdominal massage, have received more attention in recent years. In this study, a rat model of IBS with diarrhea (IBS-D) was established by instillation of acetic acid from the colon. The effects of abdominal massage on changes in gut motility, visceral hypersensitivity, and the possible mechanism were investigated. Continuous abdominal massage could decrease the stool consistency score and increase the efflux time of glass beads compared with model groups, while also decreasing mast cell counts in IBS-D rats. The mRNA and protein expressions of neuronal nitric oxide synthase (nNOS), choline acetyl transferase (CHAT), and protein gene product 9.5 (PGP9.5) were significantly upregulated by continuous abdominal massage compared with model groups. Continuous abdominal massage also improved the ultrastructure of enteric glial cells (EGCs) by decreasing the number of mitochondria and increasing the level of the heterochromatin. Meanwhile, continuous abdominal massage could upregulate the expression of glial cell line-derived neurotrophic factor (GDNF) and P-Akt/Akt. Furthermore, it could reduce visceral hypersensitivity and improve the IBS-D symptoms by regulating the phosphoinositide 3-kinase (PI3K)-Akt pathway, which would provide a novel method for the treatment of IBS-D in the clinical setting.

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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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Modulation of enteric neurons by interleukin‐6 and corticotropin‐releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

The Journal of Physiology ◽

10.1113/jphysiol.2014.279968 ◽

2014 ◽

Vol 592 (23) ◽

pp. 5235-5250 ◽

Cited By ~ 38

Author(s):

Maria M. Buckley ◽

Ken D. O'Halloran ◽

Mark G. Rae ◽

Timothy G. Dinan ◽

Dervla O'Malley

Keyword(s):

Irritable Bowel Syndrome ◽

Rat Model ◽

Interleukin 6 ◽

Colonic Motility ◽

Corticotropin Releasing Factor ◽

Visceral Hypersensitivity ◽

Enteric Neurons ◽

Irritable Bowel

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Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome

Neurogastroenterology & Motility ◽

10.1111/j.1365-2982.2006.00771.x ◽

2006 ◽

Vol 18 (7) ◽

pp. 539-546 ◽

Cited By ~ 57

Author(s):

j. h. park ◽

p-l. rhee ◽

g. kim ◽

j. h. lee ◽

y-h. kim ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Visceral Hypersensitivity ◽

Enteroendocrine Cell ◽

Cell Counts ◽

Irritable Bowel

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Antinociceptive effect of VSL#3 on visceral hypersensitivity in a rat model of irritable bowel syndrome: a possible action through nitric oxide pathway and enhance barrier function

Molecular and Cellular Biochemistry ◽

10.1007/s11010-011-1126-5 ◽

2011 ◽

Vol 362 (1-2) ◽

pp. 43-53 ◽

Cited By ~ 31

Author(s):

Cong Dai ◽

Stefano Guandalini ◽

De-Hui Zhao ◽

Min Jiang

Keyword(s):

Nitric Oxide ◽

Irritable Bowel Syndrome ◽

Rat Model ◽

Barrier Function ◽

Antinociceptive Effect ◽

Visceral Hypersensitivity ◽

Irritable Bowel ◽

Nitric Oxide Pathway

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Miltefosine treatment reduces visceral hypersensitivity in a rat model for irritable bowel syndrome via multiple mechanisms

Scientific Reports ◽

10.1038/s41598-019-49096-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Sara Botschuijver ◽

Sophie A. van Diest ◽

Isabelle A. M. van Thiel ◽

Rafael S. Saia ◽

Anne S. Strik ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Rat Model ◽

Visceral Hypersensitivity ◽

Irritable Bowel

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Electroacupuncture Relieves Visceral Hypersensitivity by Inactivating Protease-Activated Receptor 2 in a Rat Model of Postinfectious Irritable Bowel Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7048584 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Wanli Xu ◽

Mengqian Yuan ◽

Xiaoliang Wu ◽

Hao Geng ◽

Lu Chen ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Rat Model ◽

Analgesic Effect ◽

Molecular Mechanisms ◽

Critical Role ◽

Visceral Hypersensitivity ◽

Mrna Levels ◽

Irritable Bowel ◽

Protease Activated Receptor 2 ◽

Postinfectious Irritable Bowel Syndrome

Background. The role of protease-activated receptor 2 (PAR2) in the analgesic effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in postinfectious irritable bowel syndrome (PI-IBS) has yet to be elucidated. Aim. In this study, we investigated the molecular mechanisms underlying the analgesic effect of EA in a rat model of PI-IBS. Methods. Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex test before and after administration of the PAR2 agonist, PAR2-AP, and/or EA. The protein expression and mRNA levels of PAR2, CGRP, SP, and TPSP in colon tissues were measured by immunofluorescence, western blot, and RT-PCR. Results. We found that EA could alleviate VH and significantly decrease protein and mRNA levels of PAR2, TPSP, CGRP, and SP in PI-IBS rats. The analgesic effect of EA on VH was slightly reduced in the presence of PAR2-AP. Conclusions. These results suggest that EA alleviates VH symptoms through downregulation of the levels of the TPSP/PAR2/SP/CGRP signaling axis in colon tissues in PI-IBS rats. Together, our data suggests that PAR2 plays a critical role in the analgesic effect of EA on VH in PI-IBS.

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