Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats.

Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.

Melanosis coli: A factor not associated with histological progression of colorectal polyps.

OBJECTIVE: In this study we aimed to investigate the association of melanosis coli (MC) and the colorectal polyp detection rate (PDR). METHODS: In all, 1104 MC patients and 62 181 non-MC participants were enrolled. And 2208 controls were matched by participants' age and gender, and quality of bowel preparation using the propensity score matching (PSM) method. Additionally, 490 polyps in MC and 980 in controls matched by age and gender, and size and location of polyps were analyzed. The association of PDR and pathological features of polyps with MC were also analyzed. RESULTS: MC patients showed a higher PDR (44.3% vs 39.3%, P = 0.006) and detection rate of low-grade adenoma (45.4% vs 36.7%, P = 0.002) but fewer large polyps (≥10 mm) (18.8% vs 26.9%, P = 0.001), fewer polyps in the left colon (33.5% vs 40.0%, P = 0.018), and a lower detection rate of advanced adenoma/adenocarcinoma (17.4% vs 24.3%, P = 0.003) than the matched controls. On multivariate logistic regression analysis, MC was independently associated with an increased PDR (odds ratio 1.184, 95% confidence interval 1.045-1.343, P = 0.008). Analysis targeting polyps showed that there were significant differences in age, gender, location, and pathology (P < 0.001) between polyps with and without MC. However, after adjusting for participants' age and gender, size and location of polyps, there was no difference between the two groups in pathology (P = 0.635). CONCLUSION: MC is independently associated with increased colorectal PDR, but not with histological progression of polyps.

Efficacy of Endoscopic Radiofrequency Ablation for Treatment of Reflux Hypersensitivity: A Study Based on Rome IV Criteria.

Objective: Effective therapies for reflux hypersensitivity are lacking. Endoscopic radiofrequency ablation may reduce the sensitivity of the distal esophagus through direct interference with nociceptors or vagal afferent fibers and thus may be useful in reflux hypersensitivity. The aim of this study is to assess the effectiveness and possible mechanisms of endoscopic radiofrequency ablation in reflux hypersensitivity patients. Methods: Patients with reflux hypersensitivity who fulfilled the Rome IV criteria and who wished to receive further treatment were recruited. Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction. Data were collected by questionnaire using a 6-point Likert scale. The primary outcome measure was effect on symptoms including heartburn, regurgitation, and chest pain. The secondary outcomes were degree of satisfaction, medication use, acid exposure time (AET), low esophageal sphincter (LES) pressure, and total reflux episodes. We also assessed positive cell density of transient receptor potential vanilloid type 1 receptor (TRPV1) and calcitonin gene-related peptide (CGRP), both of which are biomarkers of afferent fibers, in biopsies obtained from esophageal mucosa 0.5 cm-1 cm above the Z line. These scales will be administered at baseline, 3-month follow-up, 6-month follow-up, and 12-month follow-up. Results: A total of 22 reflux hypersensitivity patients were enrolled (14 males, median age 50.0 years). A significant improvement in symptom scores (heartburn, regurgitation, and chest pain) was noted at 3 months, 6 months, and 12 months (P < 0.001). Satisfaction with life increased to 72.7% (16/22), 72.7% (16/22), and 68.2% (15/22) at 3, 6, and 12 mo, respectively, compared with baseline (P < 0.001). Nineteen patients reduced their medication use after treatment. Of these, 22.7% (5/22), 31.8% (7/22), and 40.9% (9/22) subjects stopped medication use at 3 mo, 6 mo, and 12 mo, respectively. No statistical differences were noted in AET, LES pressure, or total reflux episodes from preoperation to 12 mo postoperation. After treatment, the positive cell density of both TRPV1 and CGRP decreased significantly; however, only TRPV1 had a positive correlation with heartburn (r = 0.51, P = 0.03) and chest pain (r = 0.77, P < 0.01). Conclusion: Endoscopic radiofrequency ablation was an effective and safe therapeutic option in reflux hypersensitivity patients. Further studies with large sample size are required to validate the role of radiofrequency in reflux hypersensitivity.