Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome

2007 ◽  
Vol 292 (3) ◽  
pp. G849-G856 ◽  
Author(s):  
Tian-Hua Ren ◽  
Justin Wu ◽  
David Yew ◽  
Eric Ziea ◽  
Lixing Lao ◽  
...  

Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of c- fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2–21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semiquantitative analysis of c- fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c- fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.

Author(s):  
Maria Giuliana Vannucchi ◽  
Stefano Evangelista

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animals models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
L. D. Wang ◽  
J. M. Zhao ◽  
R. J. Huang ◽  
L. Y. Tan ◽  
Z. H. Hu ◽  
...  

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.


2020 ◽  
Vol 16 ◽  
pp. 174480692091805 ◽  
Author(s):  
Rui-Xia Weng ◽  
Wei Chen ◽  
Jia-Ni Tang ◽  
Qian Sun ◽  
Meng Li ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaofang Lu ◽  
Shengsheng Zhang ◽  
Cheng Yang ◽  
Zhengfang Wang ◽  
Luqing Zhao ◽  
...  

TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (ΔIsc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl−orHCO3-or basolateral Na+or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na+-K+-2Cl−cotransporter (NKCC),Na+-HCO3-cotransporter,Cl-/HCO3-exchanger, K+channel, or Na+/K+-ATPase, respectively, there was no difference in 5-HT-inducedΔIscamong the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl−andHCO3-secretion, possibly mediated by the combined action of CFTR, NKCC, Na+-HCO3-cotransporter,Cl-/HCO3-exchanger, K+channel, and Na+/K+-ATPase.


2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Eduardo E. Valdez-Morales ◽  
Tonatiuh Barrios-García ◽  
Alma Barajas-Espinosa ◽  
Raquel Guerrero Alba

Author(s):  
Huan-Hwa Chen ◽  
Chich-Hsiu Hung ◽  
Ai-Wen Kao ◽  
Hsiu-Fen Hsieh

Irritable bowel syndrome (IBS) is a common recurrent functional gastrointestinal disorder that impacts on patients physically and mentally. Studies on IBS have focused on adults, yet few studies have examined IBS among female university students. The aim of this study was to investigate the prevalence of IBS for female university students and its related factors. Using a cross-sectional study design, a total of 2520 female university students were recruited in southern Taiwan. The structured questionnaires, including the Rome III IBS diagnostic questionnaire, IBS symptom severity scale, Perceived Stress Scale, and World Health Organization Quality of Life BREF questionnaire (WHOQOL-BREF) were used for data collection. A total of 1894 female students complete the questionnaires. The response rate was 75.15%. The results indicated 193 female students with IBS and the prevalence of IBS was 10.1%. IBS female students had higher levels of stress and lower QOL than non-IBS female students. The risk factors for female university students developing IBS were dysmenorrhea, food avoidance, class absenteeism, and the lower physical domain of QOL. It is advised to consider these factors when providing students with counselling and relevant services in the expectation of alleviating their IBS symptoms, reducing the incidence rate of IBS, and further improving their QOL.


2006 ◽  
Vol 10 (S1) ◽  
pp. S133b-S133
Author(s):  
G.H. Song ◽  
C.H. Wilder-Smith ◽  
V. Venkatraman ◽  
K.Y. Ho ◽  
M. Chee ◽  
...  

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