scholarly journals Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

2017 ◽  
Vol 43 (2) ◽  
pp. 518-530 ◽  
Author(s):  
Yuqing Mao ◽  
Zhengyang Li ◽  
Kan Chen ◽  
Huafang Yu ◽  
Shaoren Zhang ◽  
...  

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.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fang Zhang ◽  
Zhe Ma ◽  
Zhijun Weng ◽  
Min Zhao ◽  
Handan Zheng ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bo Li ◽  
Xiong-Fei Luo ◽  
Si-Wen Liu ◽  
Na Zhao ◽  
Hua-Nan Li ◽  
...  

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sara Botschuijver ◽  
Sophie A. van Diest ◽  
Isabelle A. M. van Thiel ◽  
Rafael S. Saia ◽  
Anne S. Strik ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wanli Xu ◽  
Mengqian Yuan ◽  
Xiaoliang Wu ◽  
Hao Geng ◽  
Lu Chen ◽  
...  

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.


2020 ◽  
Vol 158 (6) ◽  
pp. S-900
Author(s):  
Nikita Hanning ◽  
Samuel Van Remoortel ◽  
Hannah Ceuleers ◽  
Heiko U. De Schepper ◽  
Annemieke Smet ◽  
...  

2009 ◽  
Vol 5 ◽  
pp. 1744-8069-5-44 ◽  
Author(s):  
Guang-Yin Xu ◽  
John H Winston ◽  
Mohan Shenoy ◽  
Shufang Zhou ◽  
Jiande DZ Chen ◽  
...  

2021 ◽  
Vol 139 ◽  
pp. 111649
Author(s):  
Tsukasa Nozu ◽  
Saori Miyagishi ◽  
Masatomo Ishioh ◽  
Kaoru Takakusaki ◽  
Toshikatsu Okumura

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