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

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.

scholarly journals Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
L. D. Wang ◽  
J. M. Zhao ◽  
R. J. Huang ◽  
L. Y. Tan ◽  
Z. H. Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Regulatory Function ◽  
Visceral Hyperalgesia ◽  
Spinal Dorsal ◽  
Dorsal Horns ◽  
Irritable Bowel

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCεprotein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCεin the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCεin spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCεof spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome

2012 ◽  
Vol 303 (2) ◽  
pp. G141-G154 ◽  
Author(s):  
D. Keszthelyi ◽  
F. J. Troost ◽  
A. A. Masclee
Keyword(s):  
Irritable Bowel Syndrome ◽  
Brain Imaging ◽  
Visceral Pain ◽  
Gastrointestinal Disorder ◽  
Visceral Hypersensitivity ◽  
Visceral Perception ◽  
Optimal Method ◽  
Flexor Reflex ◽  
Sensory Stimuli ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a “biological hallmark” for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms “assessment of visceral pain/visceral nociception/visceral hypersensitivity” and “irritable bowel syndrome.” Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

Electroacupuncture Relieves Irritable Bowel Syndrome by Regulating IL-18 and Gut Microbial Dysbiosis in a Trinitrobenzene Sulfonic Acid-Induced Post-Inflammatory Animal Model

2020 ◽  
Vol 48 (01) ◽  
pp. 77-90 ◽  
Author(s):  
Ya-Fang Song ◽  
Li-Xia Pei ◽  
Lu Chen ◽  
Hao Geng ◽  
Meng-Qian Yuan ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Sulfonic Acid ◽  
Visceral Pain ◽  
Fecal Microbiota ◽  
Visceral Hypersensitivity ◽  
Trinitrobenzene Sulfonic Acid ◽  
Model Group ◽  
Microbial Dysbiosis ◽  
Colorectal Distention ◽  
Irritable Bowel

Post inflammatory irritable bowel syndrome (PI-IBS), a subset of IBS, is characterized by symptoms of visceral pain, bloating, and changed bowel habits that occur post initial episode of intestinal infection. Gut microbial dysbiosis or inflammation plays a key role in the pathogenesis of abdominal hypersensitivity of PI-IBS. Electroacupuncture (EA) stimulation results in an alleviated PI-IBS-associated symptom. This study investigated the effect of EA on IL-18 and gut microbial dysbiosis in one visceral hypersensitive rat models with PI-IBS. A trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity rat model was developed. EA stimulation was applied to the ST25 and ST36 acupoints. Animals were assessed using abdominal withdrawal reflex (AWR) scores to determine the development of colonic visceral hypersensitivity. The 16S rRNA was used to correlate microbial diversity. IL-18 expression in colon was quantified by quantitative real-time PCR and western blotting. We identified that model rats had an increased visceral hypersensitivity to colorectal distention at different distention pressures compared with the normal group. Sensitivity to colorectal distention decreased after EA stimulation. The composition of the fecal microbiota was different between groups. Specifically, in the model group Empedobacter, Psychrobacter, Enterococcus, Butyricimonas, Vampirovibrio, Kurthia, Intestinimonas, Neisseria, Falsiporphyromonas, Bilophila, Fusobacterium, Alistipes, Veillonella, Flavonifractor, Clostridium XlVa were more abundant affected genera, whereas Lactobacillus was enriched in normal rats. EA stimulation was correlated with significant decrease in the phyla of Fusobacteria. The mRNA and protein levels of IL-18 were higher in the model group. Meanwhile, EA stimulation attenuated this response. In a word, our findings suggest that PI-IBS is associated with significant increase in IL-18 levels as well as an alteration in microbiome diversity. These changes can be reversed with EA treatment. EA stimulation has a positive effect in alleviating symptoms of visceral hypersensitivity and protecting the gastrointestinal tract.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bo Li ◽  
Xiong-Fei Luo ◽  
Si-Wen Liu ◽  
Na Zhao ◽  
Hua-Nan Li ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Visceral Hypersensitivity ◽  
Gut Motility ◽  
Choline Acetyl Transferase ◽  
Cell Counts ◽  
Enteric Glial Cells ◽  
Abdominal Massage ◽  
Phosphoinositide 3 Kinase ◽  
Irritable Bowel

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.

scholarly journals Targeting spinal TRAF6 expression attenuates chronic visceral pain in adult rats with neonatal colonic inflammation

2020 ◽  
Vol 16 ◽  
pp. 174480692091805 ◽  
Author(s):  
Rui-Xia Weng ◽  
Wei Chen ◽  
Jia-Ni Tang ◽  
Qian Sun ◽  
Meng Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Colonic Inflammation ◽  
Spinal Dorsal ◽  
Irritable Bowel

Background Irritable bowel syndrome is one of the most common gastrointestinal disorders. It is featured by abdominal pain in conjunction with altered bowel habits. However, the pathophysiology of the syndrome remains largely unknown. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be involved in neuropathic pain. The aim of this study was to investigate roles and mechanisms of TRAF6 in the chronic visceral hypersensitivity. Methods Visceral hypersensitivity was induced by neonatal colonic inflammation and was identified by colorectal distention. The protein level, RNA level, and cellular distribution of TRAF6 and its related molecules were detected with Western blot, quantitative polymerase chain reaction, and immunofluorescence. In vitro spinal cord slice recording technique was performed to determine the synaptic transmission activities. Results Neonatal colonic inflammation rats displayed visceral hypersensitivity at the age of six weeks. The expression of TRAF6 was obviously upregulated in spinal cord dorsal horn of neonatal colonic inflammation rats at the age of six weeks. Immunofluorescence study showed that TRAF6 was dominantly expressed in spinal astrocytes. Intrathecal injection of TRAF6 small interfering RNA (siRNA) significantly reduced the amplitude of spontaneous excitatory postsynaptic currents at the spinal dorsal horn level. Furthermore, knockdown of TRAF6 led to a significant downregulation of cystathionine β synthetase expression in the spinal dorsal horn of neonatal colonic inflammation rats. Importantly, intrathecal injection of TRAF6 siRNA remarkably alleviated visceral hypersensitivity of neonatal colonic inflammation rats. Conclusions Our results suggested that the upregulation of TRAF6 contributed to visceral pain hypersensitivity, which is likely mediated by regulating cystathionine β synthetase expression in the spinal dorsal horn. Our findings suggest that TRAF6 might act as a potential target for the treatment of chronic visceral pain in irritable bowel syndrome patients.

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

2019 ◽  
Vol 9 (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

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

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
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.

Mo1571 INTRARECTAL ADMINISTRATION OF A TRPV4 ANTAGONIST IMPROVES POST-INFLAMMATORY VISCERAL HYPERSENSITIVITY IN A RAT MODEL FOR IRRITABLE BOWEL SYNDROME

2020 ◽  
Vol 158 (6) ◽  
pp. S-900
Author(s):  
Nikita Hanning ◽  
Samuel Van Remoortel ◽  
Hannah Ceuleers ◽  
Heiko U. De Schepper ◽  
Annemieke Smet ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Visceral Hypersensitivity ◽  
Irritable Bowel ◽  
Intrarectal Administration
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