Rectal Hypersensitivity Research Articles

S734 Validation of Detecting Rectal Hypersensitivity According to London and ANMS/ESNM Protocols Using the Office-Based, Point-of-Care Rectal Expulsion Device (RED) in Patients With Chronic Constipation: Clinical Trial

S734 Validation of Detecting Rectal Hypersensitivity According to London and ANMS/ESNM Protocols Using the Office-Based, Point-of-Care Rectal Expulsion Device (RED) in Patients With Chronic Constipation: Clinical Trial

Translational evaluation of Gelsectan® effects on gut barrier dysfunction and visceral pain in animal models and irritable bowel syndrome with diarrhoea.

Gelsectan® is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan® on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions. Animals: Wistar rats received gavage with XOS, XG+PPGS or XG+PPGS+XOS, as a single dose or for 7days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively. Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG+PPGS+XOS failed to reverse PRS, but 7days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan® treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan® restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan® treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D. Gelsectan® prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan® can be considered as an effective therapy for IBS-D symptoms.

Review article: advances in the diagnosis and management of anorectal motility disorders.

Anorectal motility disorders such as dyssynergic defecation (DD), faecal incontinence (FI) and anorectal pain affect 40% of the population and are a frequent reason for gastroenterology consultation. They significantly affect the quality of life and lead to psychological distress. Lack of understanding of these problems compounded by a lack of availability and knowledge of diagnostic tools in most medical centres and/or trained physicians has significantly hampered this field. To discuss the latest advances in pathophysiology, diagnostic tests and therapeutic options for these disorders using an evidence-based approach. We reviewed the published literature over the past 20 years on DD, FI and anorectal pain and distilled these into a narrative review. A detailed history, prospective stool diary and digital rectal exam, together with diagnostic tests such as anorectal manometry, balloon expulsion test, translumbosacral anorectal magnetic stimulation test for assessing neuropathy, defecography and anal ultrasound, can provide detailed mechanistic and structural information. Such knowledge can pave the way for a meaningful and pathophysiologic-based management approach. This could include biofeedback therapy for DD or FI, sensory training for rectal hyposensitivity or sensory adaptation training for rectal hypersensitivity or sphincter bulking agents or neuromodulation therapies. These treatments are effective and safe. Anorectal motility disorders are common, but either less well recognized or poorly managed by most gastroenterologists. Equipped with the practical and up-to-date knowledge provided in this review, physicians could provide improved health care for these patients.

Rapid-Onset, Short-Duration Induction of Colorectal Contractions in Anesthetized, Adult, Male Rats.

Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal chemoreceptors and mechanoreceptors and are involved in various rectal hypersensitivity disorders with common features of colorectal overactivity. These stimulatory properties of TRPV1 receptors on colorectal function suggested that brief stimulation of TRPV1 might provide a means of pharmacologically activating the colorectum to induce defecation in patients with an "unresponsive" colorectum. The current studies explored the basic features of TRPV1 receptor-induced contractions of the colorectum in anesthetized rats with and without acute spinal cord injury (aSCI). Cumulative concentration-response curves to intrarectal (IR) capsaicin (CAP) solutions (0.003%-3.0%) were performed in anesthetized aSCI and spinal intact rats. CAP produced an "inverted U," cumulative concentration-response curve with a threshold for inducing colorectal contractions at 0.01% and a peak response at 0.1% and slight decreases in responses up to 3%. Decreases in responses with concentrations >0.1% are due to a rapid desensitization (i.e., ≤30 minutes) of TRPV1 receptors to each successive dose. Desensitization appeared fully recovered within 24 hours in spinal intact rats. Colorectal contractions were completely blocked by atropine, indicating a reflexogenic activation of parasympathetic neurons, and responses were completely unaffected by a neurokinin 2 receptor antagonist, indicating that release of neurokinin A from afferent terminals and subsequent direct contractions of the smooth muscle was not involved. IR administration of three other TRPV1 receptor agonists produced similar results as CAP. SIGNIFICANCE STATEMENT: Individuals with spinal cord injury often lose control of defecation. Time-consuming bowel programs using digital stimulation of the rectum are used to empty the bowel. This study shows that intrarectal administration of the transient receptor potential vanilloid 1 (TRPV1) receptor agonist, capsaicin, can induce rapid-onset, short-duration colorectal contractions capable of inducing defecation in spinal cord injured and intact rats. Therefore, TRPV1 agonists show promise as potential therapeutics to induce defecation in individuals with neurogenic bowel.

The impact of transcutaneous electrical acustimulation (TEA) on rectal distension-induced pain in patients with irritable bowel syndrome (IBS)-A study to determine the optimal TEA delivery modalities and effects on rectal sensation and autonomic function.

Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function. Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment. Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04). TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

High-resolution anorectal manometry in children.

Anorectal manometry is one of the motility tests in children performed by pediatric gastroenterologist. It evaluates the motility function of anorectal tract. It is helpful for diagnosing children with constipation, rectal hypersensitivity, fecal incontinence, Hirschsprung disease, anal achalasia, and anorectal malformations. The most common indication to perform anorectal manometry is to diagnose Hirschsprung disease. It is a safe procedure. This paper discusses recent advances and reviews on anorectal motility disorders in children.

Factors influencing rectal hypersensitivity in irritable bowel syndrome: A systematic review and meta-analysis.

A frequent, although not universal, feature of irritable bowel syndrome (IBS) is heightened sensitivity to mechanical stimulation of the rectum, termed rectal hypersensitivity (RH). Differences in RH-based on sex, IBS subtype, IBS diagnostic criteria and age of population studied are incompletely understood. We aimed to determine whether IBS population had lower pain thresholds than healthy controls. We searched MEDLINE and EMBASE databases (1970-2021). Prospective studies that compared pain/discomfort thresholds to mechanical rectal stimuli in IBS and healthy controls were included. Data were pooled for meta-analyses and effect sizes were calculated with 95% confidence interval (CIs). Our search strategy identified 809 studies of which 32 studies met the inclusion criteria. Reduced rectal pain thresholds was more common in IBS patients compared to healthy controls with an effect size of 1.00 95% CIs (0.77-1.24) (p< 0.0001) (I2 = 78.6%). The pediatric IBS population had lower pain thresholds than adult IBS populations (p= 0.05) but no difference based on IBS diagnostic criteria, subtype or sex. The results suggest that reduced rectal pain threshold to experimental stimulation is far more common in IBS patients than healthy controls. Further research is required to understand the pathophysiological and therapeutic implications of rectal sensitivity such as its role in measuring response to treatment and prognosis in IBS.

Type of Rectal Barostat Protocol Affects Classification of Hypersensitivity and Prediction of Symptom Severity in Irritable Bowel Syndrome.

Background/AimsVisceral hypersensitivity is an important pathophysiologic mechanism in irritable bowel syndrome (IBS). We compared 2 barostat distension protocols and their ability to distinguish between IBS patients and healthy controls, identify subjects with rectal hypersensitivity, and their associations with gastrointestinal symptom severity.MethodsWe retrospectively reviewed all patients at our unit that had undergone barostat investigations 2002-2014. Protocol 1 (n = 369) used phasic isobaric distensions with stepwise increments in pressure and protocol 2 (n = 153) used pressure controlled ramp inflations. Both protocols terminated when subjects reported pain or maximum pressure was reached. Thresholds for first sensation, urgency, discomfort and pain were established. Age- and gender-matched controls were used for comparison. The gastrointestinal symptom rating scale–IBS, and the hospital anxiety and depression scale were used for symptom reports.ResultsA significantly higher proportion of patients was classified as having hypersensitivity in protocol 1 vs protocol 2 for all thresholds (P < 0.001). Patients with visceral hypersensitivity, defined based on rectal pain thresholds in protocol 1 had more severe gastrointestinal symptoms overall as well as anxiety, whereas these associations were weaker or in most cases absent when visceral hypersensitivity was defined based on rectal pain thresholds in protocol 2.ConclusionOur study indicates that a rectal barostat protocol using phasic isobaric distensions with stepwise pressure increments is more sensitive in IBS patients with respect to identifying subjects with rectal hypersensitivity and a link with IBS symptoms.

Systematic review and meta-analysis of anal motor and rectal sensory dysfunction in male and female patients undergoing anorectal manometry for symptoms of faecal incontinence.

AimManometry is the best established technique to assess anorectal function in faecal incontinence. By systematic review, pooled prevalences of anal hypotonia/hypocontractility and rectal hypersensitivity/hyposensitivity in male and female patients were determined in controlled studies using anorectal manometry.MethodsSearches of MEDLINE and Embase were completed. Screening, data extraction and bias assessment were performed by two reviewers. Meta‐analysis was performed based on a random effects model with heterogeneity evaluated by I 2.ResultsOf 2116 identified records, only 13 studies (2981 faecal incontinence patients; 1028 controls) met the inclusion criteria. Anal tone was evaluated in 10 studies and contractility in 11; rectal sensitivity in five. Only three studies had low risk of bias. Pooled prevalence of anal hypotonia was 44% (95% CI 32–56, I 2 = 96.35%) in women and 27% (95% CI 14–40, I 2 = 94.12%) in men. The pooled prevalence of anal hypocontractility was 69% (95% CI 57–81; I 2 = 98.17%) in women and 36% (95% CI 18–53; I 2 = 96.77%) in men. Pooled prevalence of rectal hypersensitivity was 10% (95% CI 4–15; I 2 = 80.09%) in women and 4% (95% CI 1–7; I 2 = 51.25%) in men, whereas hyposensitivity had a pooled prevalence of 7% (95% CI 5–9; I2 = 0.00%) in women compared to 19% (95% CI 15–23; I 2 = 0.00%) in men.ConclusionsThe number of appropriately controlled studies of anorectal manometry is small with fewer still at low risk of bias. Results were subject to gender differences, wide confidence intervals and high heterogeneity indicating the need for international collective effort to harmonize practice and reporting to improve certainty of diagnosis.

P024 Anorectal Manometry in Patients with Fecal Incontinence After Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease: A Cohort Study.

Fecal incontinence (FI) affects up to 1 in 4 patients with inflammatory bowel disease (IBD) and is associated with inflammation, surgeries, and altered rectal sensitivity. Ileal pouch-anal anastomosis (IPAA) is a surgical intervention for select IBD patients to avoid a permanent stoma. High-resolution anorectal manometry (HRAM) studies in IBD patients with FI demonstrate lower resting pressures and rectal sensory dysfunction. However, HRAM data in IBD patients with FI post-IPAA remains limited. We hypothesized patients with FI would have lower resting and squeeze pressures and rectal hypersensitivity compared to healthy controls and that these changes would be similar after IPAA. Retrospective review of prospectively collected data was conducted on patients undergoing HRAM from 2017-2021 at a single urban academic medical center. Patient characteristics (age, gender, BMI, stool frequency, diabetes, pregnancy history) and surgical history (prior perianal surgery, index vs. re-do IPAA) were obtained. HRAM variables included rectoanal inhibitory reflex (RAIR), sphincter length, resting, squeeze, cough, and push pressures, sensation thresholds (first sensation, constant sensation, desire to defecate, urgency to defecate, max tolerable volume), and balloon expulsion test (BET). HRAM outcomes in IPAA patients with FI (IPAA-FI) were compared to non-IBD patients with FI (non-IBD-FI). HRAM data for both patient cohorts were also compared to existing normative data of healthy controls. Non-IBD patients with constipation and FI were excluded from analysis. An independent samples t-test was performed (p < 0.05) for continuous variables, and chi-square test was used for categorical variables. Fifty-six patients (66% female) were in the non-IBD-FI group. Eighteen patients (67% female) were in the IPAA-FI group. Average age in the IPAA-FI cohort was 44.8 ± 13.6 vs. 66.3 ± 14.4 in the non-IBD-FI group (p< 0.01). Sphincter length in the IPAA-FI group was 2.7 ± 1.1cm vs. 3.2 ± 0.6cm in the non-IBD-FI group (p=0.03). There was no significant difference in sensation thresholds or resting, squeeze, cough, and push pressures between the two groups. Urinary incontinence was observed in 5.6% of IPAA-FI patients vs. 44.6% of non-IBD-FI patients (p < 0.01). RAIR was present in 38.5% of IPAA-FI patients vs. 100% of non-IBD-FI patients (p < 0.01). Both patient cohorts had significantly shorter sphincter length, lower squeeze and push pressures, and lower sensation thresholds compared to normative data. Resting pressures for the IPAA-FI group was not significantly different compared to healthy controls. Overall, anorectal pressures and sensation are similar between IPAA-FI and non-IBD-FI patients. However, the underlying FI mechanism seems to differ. Higher rates of urinary incontinence in the non-IBD-FI cohort suggests global pelvic floor dysfunction compared to IPAA-FI patients who are younger and have post-operative neuromuscular dysfunction, as evidenced by shorter sphincter length and absent RAIR. Though rectal hypersensitivity and lower squeeze/push pressures are observed in both patient groups compared to healthy controls, normal resting pressure in IPAA-FI suggests that potentially different normative ranges are needed for this cohort to accurately assess post-surgical changes and guide pre-operative counseling.

Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression.

Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P<0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P=0.0007) and pain (P=0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r=0.51, FDR=0.01), and inversely with first rectal sensation (r=-0.48, FDR=0.01) and pain (r=-0.41, FDR=0.02) thresholds. Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS.

Sensory Adaptation Training or Escitalopram for IBS With Constipation and Rectal Hypersensitivity: A Randomized Controlled Trial.

INTRODUCTION:Rectal hypersensitivity is an important pathophysiological dysfunction in irritable bowel syndrome with predominant constipation (IBS-C), whose treatment remains challenging. In a randomized controlled trial, we compared the efficacy and safety of a novel sensori-behavioral treatment, sensory adaptation training (SAT) with escitalopram.METHODS:Patients with IBS-C (Rome III) with rectal hypersensitivity received 6 biweekly sessions of SAT or escitalopram 10 mg daily for 3 months. SAT was performed by repetitive gradual distension of 10-cm long highly compliant rectal balloon above tolerability thresholds using barostat. Treatment effects on sensory thresholds and symptoms were compared. Coprimary outcome measures were those achieving improvements in rectal hypersensitivity (≥20% increase in ≥2/3 sensory thresholds) and pain (≥30% decrease).RESULTS:We randomized 49 patients; 26 received SAT and 23 escitalopram. SAT significantly improved desire to defecate (Δ 13.5 ± 2.3 vs 2.2 ± 1.1 mm Hg, P = 0.0006) and maximum tolerability (Δ 14.8 ± 1.9 vs 1.6 ± 0.9 mm Hg, P < 0.0001) thresholds compared with escitalopram. There were significantly greater percentage of hypersensitivity responders with SAT than escitalopram (69% vs 17%, P < 0.001), but not pain responders (58% vs 44%, P = 0.4). Daily pain scores did not differ between groups (P = 0.8) or escitalopram (P = 0.06) but decreased with SAT (P = 0.0046) compared with baseline. SAT significantly increased rectal compliance (P < 0.019) and complete spontaneous bowel movements per week than escitalopram (P = 0.04). Five withdrew from adverse events with escitalopram and none with SAT.DISCUSSION:SAT was significantly more efficacious in improving hypersensitivity and bowel symptoms in IBS-C than escitalopram. SAT is a promising novel treatment for IBS with rectal hypersensitivity.

Rectal Hypersensitivity in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Abdominal pain is a key symptom of inflammatory bowel disease (IBD), particularly in active IBD, but also occurs in patients with quiescent disease suggesting that mechanisms other than active inflammation may be responsible. Putative hypothesis to explain chronic abdominal pain in patients with quiescent IBD includes crossover with irritable bowel syndrome where rectal hypersensitivity is common and has pathophysiological implications. In contrast, in IBD, the role of rectal hypersensitivity has not been established. We aimed to determine if rectal hypersensitivity was more common in IBD compared to a healthy control population. We searched MEDLINE and EMBASE databases (1970-2018). Prospective studies that measured pain/discomfort thresholds to mechanical rectal stimuli in IBD and healthy controls were included. Data were pooled for meta-analysis and effect sizes were calculated with 95% confidence intervals (CIs). Our search strategy identified 222 citations of which 8 met the inclusion criteria, covering 133 individuals with IBD (67 men), aged between 10 and 77 compared to 99 healthy controls (55 men), aged between 10 and 67. The prevalence of rectal hypersensitivity in IBD compared to healthy controls was similar with an effect size of 0.59 (95% CIs: -0.27 to 1.44, P = .16, I 2 = 87.3%). Subgroup analysis did show a significant effect size for patients compared to healthy controls with active disease (1.32) but not for quiescent disease (-0.02). These results suggest that reduced rectal pain thresholds to experimental stimulation are not seen in IBD populations except during active flares of the disease. Further research is required to understand the pathophysiology of chronic abdominal pain in quiescent IBD populations with and without chronic abdominal pain to identify appropriate management strategies.

Transitional changes in gastrointestinal transit and rectal sensitivity from active to recovery of inflammation in a rodent model of colitis

Patients with ulcerative colitis are typically suspected of an inflammatory flare based on suggestive symptoms of inflammation. The aim of this study was to evaluate the impact of inflammation on colonic motility and rectal sensitivity from active to recovery of inflammation. Male rats were given drinking water with 5% dextran sulfate sodium for 7 days. Inflammation, intestinal motor and sensory functions were investigated weekly for 6 weeks. (1) The disease activity index score, fecal calprotectin and tumor necrosis factor alpha were increased from Day 0 to Day 7 (active inflammation) and then decreased gradually until recovery. (2) Distal colon transit was accelerated on Day 7, and then remained unchanged. Whole gut transit was delayed on Day 7 but accelerated from Day 14 to Day 42. (3) Rectal compliance was unaffected from Day 0 to Day 7, but decreased afterwards. (4) Rectal hypersensitivity was noted on Day 7 and persistent. (5) Plasma acetylcholine was decreased on Day 7 but increased from Day 14 to Day 42. Nerve growth factor was increased from Day 7 to Day 42. DSS-induced inflammation leads to visceral hypersensitivity that is sustained until the resolution of inflammation, probably mediated by NGF. Rectal compliance is reduced one week after the DSS-induced inflammation and the reduction is sustained until the resolution of inflammation. Gastrointestinal transit is also altered during and after active colonic inflammation.

Electroacupuncture at ST36 Relieves Visceral Hypersensitivity via the NGF/TrkA/TRPV1 Peripheral Afferent Pathway in a Rodent Model of Post-Inflammation Rectal Hypersensitivity.

PurposeThe aim of the study was to investigate the effects of electroacupuncture (EA) at ST36 on rectal hypersensitivity and compliance in DSS-treated post-inflammation rats. In addition, we explored the involvement of mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway.MethodsRats were provided water with 5% dextran sulphate sodium (DSS) for 7 days. Two weeks after the DSS treatment they were subjected to initial and repetitive EA. Different sets of parameters were compared in the initial test and then EA with the selected parameters were performed for 2 weeks. Rectal compliance was assessed by colorectal distension while visceral sensitivity was evaluated by abdominal withdraw reflexes (AWR) and electromyogram (EMG). Masson’s trichrome staining was performed to stain collagen and toluidine blue staining was applied to assess the degranulation of mast cells. Nerve growth factor (NGF), tryptase, TrkA and TRPV1 were measured by Western blot or immunofluorescence staining.ResultsEA at 100 Hz was more effective in improving rectal compliance and visceral hypersensitivity. Daily EA improved visceral hypersensitivity but not rectal compliance. Five weeks after DSS treatment, fibrosis was noted in both sham-EA and EA groups. The expression and activation of mast cells were significantly reduced after the 2-week EA treatment with a concurrent decrease in the expression of colonic NGF/TrkA and TRPV1 in both colon and dorsal root ganglions.ConclusionEA at ST36 with a special set of parameters has no effect on reduced rectal compliance but relieves visceral hypersensitivity via the mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway in DSS-treated post-inflammation rats.

Visceral hypersensitivity is together with psychological distress and female gender associated with severity of IBS-like symptoms in quiescent ulcerative colitis.

A subset of ulcerative colitis (UC) patients in remission demonstrate IBS-like symptoms. Visceral hypersensitivity is a key pathophysiological mechanism in IBS, but its relevance to IBS-like symptoms in inactive UC remains unclear. UC patients in remission (UCR) were screened for IBS-like symptoms. Rectal sensitivity was assessed with rectal balloon distensions, with determination of sensory thresholds and unpleasantness/pain intensity ratings. Patients completed questionnaires evaluating gastrointestinal (GI) and psychological symptoms. Age- and gender-matched IBS subjects and healthy controls (HC) also underwent a rectal sensitivity test. We included 36 UCR patients (18 with IBS-like symptoms (UCR+IBS) and 18 without (UCR-IBS)), 36 IBS subjects, and 14 HC. UCR and IBS patients were more sensitive to rectal balloon distensions than HC, but no differences between UCR and IBS patients were observed. UCR+IBS patients had lower sensory thresholds and higher unpleasantness ratings than UCR-IBS. In UCR patients, the overall GI symptom severity, pain, and bloating, but not diarrhea, constipation or satiety, were associated with rectal sensitivity. In multivariate analyses, rectal sensitivity, psychological distress, and female gender were identified as factors independently associated with GI symptom severity. 61% of UCR patients demonstrated rectal hypersensitivity, and these patients more commonly reported at least mild bloating and pain, and overall GI symptoms, compared to those with normal rectal sensitivity. Visceral hypersensitivity was associated with IBS-like symptoms, in particular pain and bloating, in inactive UC. Together with psychological factors and female gender, visceral hypersensitivity seems to be involved in GI symptom generation in quiescent UC.

S0458 Does Fecal Incontinence Symptom Severity Evaluated by Symptom Summation and Individual Fecal Incontinence Components Predict Rectal Hypersensitivity in a Large Fecal Incontinence Cohort?

INTRODUCTION: Rectal sensation contributes significantly to the process of continence. Rectal hypersensitivity (RH) has been associated with a greater perception to defecate, increase lifestyle restrictions, and decrease quality of life domains in patients with fecal incontinence (FI). RH to rectal sensation measurements during an anorectal manometry (ARM) are often reported by patients with FI. Our hypothesis is that higher self-reported FI symptom severity will be associated with RH. METHODS: Retrospective cross-sectional study was conducted on 955 FI patients ≥18 years of age who were referred for ARM at a single tertiary medical center from 6/11 to 3/20. All patients completed the Fecal Incontinence Severity Index (FISI) questionnaire (0–61 scale: higher scores representing greater symptom severity). FISI components, gas (0–12), mucous (0–12), liquid (0–19), and stool (0–18) were scored using the patient validated metrics instead of physician values. RH was defined as balloon distention volume documented in the FI literature: First Sensation (FS) as ≤38 ml and Urge-to-Defecate (UD) as ≤80 ml. Independent t-tests were performed to assess the mean difference of FISI summation (FISI-Sum) and FISI components (FISI-C) between FI patients categorized as RH vs. normal rectal sensation (NRS) and sex (male vs. female). A P-value of ≤0.05 was considered statistically significant. RESULTS: Demographics (N = 955) were as follows: mean age 60.4 ± 14.1 years (19–91), mean BMI 29.3 ± 6.6, 73.6% female, and 90.7% Caucasian. No demographics differences between genders. The mean FISI-Sum and FISI-C scores for entire sample were 35.8 ± 12.5: Gas (10.2 ± 2.7), Mucous (7.9 ± 3.4), Liquid (13.5 ± 4.3), and Stool (12.8 ± 3.6). RH measured by FS and UD criteria for the sample were 29.1% and 49.1%. No significant differences in FISI-Sum and FISI-C related to RH using FS besides Liquid incontinence reported greater severity by NRS (P = 0.001) (Table 1). No significant differences in FISI-Sum and FISI-C between the RH and NRS groups in males. Females in the NSR group self-reported greater Liquid incontinence (P = 0.003) vs. the RH group measured by FS and no differences between RH and NRS groups using UD. CONCLUSION: Rectal hypersensitivity did not predict FI severity and may reduce the amount of liquid FI in patients. Therefore, the use of anorectal rectal function testing including rectal sensation metrics and rectal sensory re-training are necessary for evaluating and improving defecatory sensations.Table 1

Rectal Hypersensitivity in Irritable Bowel Syndrome and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Objectives: A frequent, although not universal, feature of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), is heightened sensitivity to mechanical stimulation of the rectum, termed rectal hypersensitivity (RH). Differences in RH based on gender, IBS/IBD subtype, presence of inflammation and adult compared to paediatric populations are incompletely understood. We aimed to determine the magnitude of RH in IBS/IBD compared to healthy controls. Design: We searched MEDLINE and EMBASE databases (1970-2018). Prospective studies that compared pain/ discomfort thresholds to mechanical rectal stimuli in IBS/IBD and healthy controls were included. Data was pooled for meta-analyses and Hedges’ g effect sizes were calculated with 95% confidence interval (CIs). Results: Our search strategy identified 684 studies of which 31 studies met the IBS inclusion criteria. RH was more common in IBS patients effect size 0.97 95% CI (0.77-1.17), p < 0.0001, I2 = 77.2%. Paediatric IBS populations were more likely to be hypersensitive than adult populations (p = 0.04) but there were no differences based on diagnostic criteria, subtype or gender. In 8 studies met the IBD inclusion criteria, RH was not more common in IBD patients effect size 0.46 95% CI (-0.21-1.12), p = 0.18, I2 = 87.6% except during disease flares (p = 0.02). RH is more common in IBS than IBD populations (p = 0.0001). Conclusions: The results suggest that reduced rectal pain threshold to experimental stimulation is a marker of IBS. RH is not normally present in IBD except during active inflammation. Further research is required to understand the pathophysiological and therapeutic implications of rectal sensitivity in IBS compared to IBD. Funding Statement: AA was funded by the People Programme of the European Union’s Seventh Framework Programme under REA grant agreement no.607652 (NeuroGu). ADF was supported by the West Midlands Clinical Research Network Scholarship. Declaration of Interests: None of the authors have any conflict of interests to declare.

Fecal Urgency: Clinical and Manometric Characteristics in Patients With and Without Diarrhea.

Fecal urgency is classically associated with diarrhea, but is also common in individuals with normal bowel habits or constipation. Its etiology, particularly in non-diarrhea individuals, is unclear. We examined data from 368 individuals with and without diarrhea who underwent three-dimensional high-resolution anorectal manometry and balloon expulsion test. All patients completed the Rome III constipation module and the pelvic floor distress inventory (PDFI-20) survey. Patients were considered to have fecal urgency if they reported being bothered "moderately" or "quite a bit" by it in the past 3months. A total of 103 patients (28.0%) met our definition of fecal urgency. These patients were significantly more likely to meet criteria for irritable bowel syndrome and to report fecal incontinence, urinary incontinence, and diarrhea. Fecal urgency was associated with rectal hypersensitivity in those with diarrhea, but not in those without diarrhea. Fecal urgency was associated with urinary urge incontinence in those without diarrhea, but not those with diarrhea. In patients with diarrhea, fecal urgency is associated with rectal hypersensitivity, whereas in patients without diarrhea, fecal urgency is associated with urinary urge incontinence. This suggests that fecal urgency has different pathophysiological mechanisms in patients with different underlying bowel habits.

Randomised clinical trial: linaclotide vs placebo—a study of bi‐directional gut and brain axis

SummaryBackgroundLinaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS‐C) symptoms, but how it improves pain in humans is unknown.AimsTo investigate the effects of linaclotide and placebo on the afferent and efferent gut‐brain‐gut signalling in IBS‐C patients, in a randomised clinical trial.MethodsPatients with IBS‐C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi‐directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal‐anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto‐cortical and cortico‐rectal evoked potentials.ResultsThirty‐nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups. The efferent cortico‐anorectal and spino‐anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS‐QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13).ConclusionsLinaclotide prolongs afferent gut‐brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS‐C symptoms and QOL compared to placebo. These mechanisms may explain the effects of linaclotide on pain relief in IBS‐C patients.ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.