[Show abstract][Hide abstract] ABSTRACT: Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.
World Journal of Gastroenterology 10/2014; 20(39):14126-14131. DOI:10.3748/wjg.v20.i39.14126 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polygonum chinense Linn., a folk medicine, has long been used for the treatment of diarrhea and enteritis in southwestern China. However, the components responsible for its anti-diarrheal activity are still poorly understood.
To determine anti-diarrheal activities of P. chinense L. and to identify its active components through bioactivity-guided isolation technique.
Animals were orally administered with the extract of P. chinense L.. The anti-diarrheal effects of 75% ethanol extract, four fractions with different polarities from 75% ethanol extract, different eluates collected from Diaion HP-20 macroporous resin chromatography, ellagic acid and corilagin, were examined based on mouse models of castor oil- and magnesium sulfate-induced diarrhea.
The results showed that the 75% ethanol extract of P. chinense L. exhibited significant anti-diarrheal activities in a dose-dependent manner in two mouse models. Through in vivo bioactivity-guided fractionation processes, n-butanol and aqueous fractions were found to exhibit prominent anti-diarrheal activities, and two major compounds, ellagic acid and corilagin, from these active fractions were found to possess anti-diarrheal effects.
Present study provides evidence of the utilization of P. chinense L. for diarrhea, and ellagic acid and corilagin are two components contributing to the anti-diarrheal effect.
Journal of Ethnopharmacology 07/2013; DOI:10.1016/j.jep.2013.07.007 · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to investigate the analgesic effect of JCM-16021, a revised traditional Chinese herbal formula, on postinflammatory irritable bowel syndrome (PI-IBS) in rats. The trinitrobenzene sulfonic (TNBS) acid-induced PI-IBS model rats were orally administrated with different doses of JCM-16021 (1.2, 2.4, and 4.8 g/kg/d) for 14 consecutive days. The results showed that JCM-16021 treatment dose-dependently attenuated visceral hyperalgesia in PI-IBS rats. Further, the colonic enterochromaffin (EC) cell number, serotonin (5-HT) content, tryptophan hydroxylase expression, and mechanical-stimuli-induced 5-HT release were significantly ameliorated. Moreover, the decreased levels of mucosal cytokines in PI-IBS, especially the helper T-cell type 1- (T(h)1-) related cytokine TNF-α, were also elevated after JCM-16021 treatment. These data demonstrate that the analgesic effect of JCM-16021 on TNBS-induced PI-IBS rats may be medicated via reducing colonic EC cell hyperplasia and 5-HT availability.
Evidence-based Complementary and Alternative Medicine 06/2012; 2012:239638. DOI:10.1155/2012/239638 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the key factors in developing the trinitrobenzene sulfonic acid (TNBS)-induced post-inflammatory irritable bowel syndrome (PI-IBS) model in rats.
TNBS was administered to rats at the following conditions: (1) with different doses (20, 10, 5 mg/0.8 mL per rat); (2) with same dose in different concentrations (20 mg/rat, 25, 50 mg/mL); (3) in different ethanol percentage (25%, 50%); and (4) at depth either 4 cm or 8 cm from anus. At 5 d and 4 wk after TNBS administration, inflammation severity and inflammation resolution were evaluated. At 4 and 8 wk after TNBS application, visceral hyperalgesia and enterochromaffin (EC) cell hyperplasia were assayed by abdominal withdrawal reflex test, silver staining and capillary electrophoresis.
Our results showed that: (1) TNBS induced dose-dependent acute inflammation and inflammation resolution. At 5 d post TNBS, the pathological score and myeloperoxidase (MPO) activity in all TNBS treated rats were significantly elevated compared to that of the control (9.48 ± 1.86, 8.18 ± 0.67, 5.78 ± 0.77 vs 0, and 3.55 ± 1.11, 1.80 ± 0.82, 0.97 ± 0.08 unit/mg vs 0.14 ± 0.01 unit/mg, P < 0.05). At 4 wk post TNBS, the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control (1.52 ± 0.38 and 0.80 ± 0.35 vs 0, P < 0.05); (2) Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia. At 4 wk post TNBS, abdominal withdrawal reflex (AWR) threshold pressure in all TNBS-treated groups were decreased compared to that of the control (21.52 ± 1.73 and 27.10 ± 1.94 mmHg vs 34.44 ± 1.89 mmHg, P < 0.05). At 8 wk post TNBS, AWR threshold pressure in 8 cm administration group was still significantly decreased (23.33 ± 1.33 mmHg vs 36.79 ± 2.29 mmHg, P < 0.05); (3) Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia. In TNBS-25% ethanol-treated group, the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50% ethanol-treated group, while AWR threshold pressure were significantly elevated (36.33 ± 0.61 mmHg vs 23.33 ± 1.33 mmHg, P < 0.05); and (4) TNBS (5 mg/0.8 mL per rat, in 50% ethanol, 8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.
TNBS dosage, concentration, intracolonic administration position, and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.
World Journal of Gastroenterology 05/2012; 18(20):2481-92. DOI:10.3748/wjg.v18.i20.2481 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinically, adults who have experienced stresses in childhood present with episodes of serious symptoms of irritable bowel syndrome that are associated with acute stress, but the mechanism is not well understood. This study aimed to investigate the colonic sensory/motor responses to acute water avoidance stress (WAS) in male adult rats subjected to neonatal maternal separation (NMS), and the underlying mechanism of sensory/motor responses. Effects of the combined acute and early life stress on visceral sensation, colonic motility, and the tissue and luminal content of serotonin (5-hydroxytryptamine, 5-HT) in the proximal and distal colon were evaluated using the abdominal withdrawal reflex test, faecal pellet output measurement and capillary electrophoresis analysis, respectively. Results showed that WAS significantly increased not only visceral sensitivity but also colonic motility in NMS rats compared to the normal rats. These alterations were accompanied by significant increase in 5-HT content in the proximal but not the distal colonic tissues; these alterations were also associated with increased density of enterochromaffin (EC) cells in the proximal segment. In contrast, the faecal content of 5-HT increased similarly in both segments. Consecutive administration of parachlorophenylalanine to NMS rats was more potent at 500 mg kg⁻¹ day⁻¹ than at 150 mg kg⁻¹ day⁻¹ in suppressing colonic sensory/motor responses to WAS, corresponding to the greater reduction of the tissue and faecal content of 5-HT and of EC cell density in the colon. These data indicate that combined early life stress and acute stress effectively induce visceral hyperalgesia and motility disorder through 5-HT pathways in the colon of rats, and the proximal and distal colon have different responses towards the combined stressors.
[Show abstract][Hide abstract] ABSTRACT: Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy. PERSPECTIVE: This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS.
The journal of pain: official journal of the American Pain Society 02/2011; 12(5):600-9. DOI:10.1016/j.jpain.2010.11.005 · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Post-infectious irritable bowel syndrome (PI-IBS) is a subset of IBS which occurs after an episode of acute gastrointestinal infections. The mechanisms of PI-IBS are not fully understood. Currently, numerous animal models have been used in the study of PI-IBS. This article reviews the strengths and weaknesses of these models.
All relevant articles were identified by searching in Ovid SP from 1962, the year the term PI-IBS was coined, up to December 31, 2009. The types of model were categorized as either post-infectious or post-inflammatory, and the characteristics of each kind of model were listed.
Based on our literature search, 268 articles were identified. Of those articles, 50 were included in this review. The existing PI-IBS models include infection with bacteria (e.g., Campylobacter jejuni, Salmonella enterica, and Campylobacter rodentium), and infection with parasites (e.g., Trichinella spiralis, Nippostrongylus brasiliensis, and Cryptosporidium parvum). The post-inflammatory IBS models are commonly induced with chemical agents, such as acetic acid, deoxycholic acid, dextran sulfate sodium, mustard oil, zymosan, and trinitrobenzene sulfonic acid (TNBS). TNBS is the most commonly used agent for post-inflammatory IBS models, but the experimental protocol varies. These models have one or more aspects similar to IBS patients.
Different methods have been used for the development of post-infectious or post-inflammatory IBS models. Each model has its weaknesses and strengths. More studies are needed to establish post-infection IBS models using more common pathogens. A standard protocol in developing TNBS-induced post-inflammatory IBS model is needed.
Journal of Gastroenterology 02/2011; 46(2):164-74. DOI:10.1007/s00535-010-0321-6 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of para-chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell patch-clamp recording in pCPA-treated rats. Calcineurin and Ca(2+)-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity.
European journal of pharmacology 11/2010; 647(1-3):75-83. DOI:10.1016/j.ejphar.2010.08.019 · 2.68 Impact Factor