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Heart rate variability (HRV) has been used to measure autonomic nervous system (ANS) activity noninvasively. The purpose of this study was to identify the most suitable HRV parameters for ANS activity in response to brief rectal distension (RD) in patients with Irritable Bowel Syndrome (IBS). IBS patients participated in a five-session study. During each visit, an ECG was recorded for 15 min for baseline values and during rectal distension. For rectal distension, a balloon was inflated in the rectum and the pressure was increased in steps of 5 mmHg for 30 s; each distension was followed by a 30 s rest period when the balloon was fully deflated (0 mmHg) until either the maximum tolerance of each patient was reached or up to 60 mmHg. The time-domain, frequency-domain and nonlinear HRV parameters were calculated to assess the ANS activity. The values of each HRV parameter were compared between baseline and RD for each of the five visits as well as for all five visits combined. The sensitivity and robustness/reproducibility of each HRV parameter were also assessed. The parameters included the Sympathetic Index (SI); Root Mean Square of Successive Differences (RMSSD); High-Frequency Power (HF); Low-Frequency Power (LF); Normalized HF Power (HFn); Normalized LF Power (LFn); LF/HF; Respiratory Sinus Arrhythmia (RSA); the Poincare Plot's SD1, SD2 and their ratio; and the pNN50, SDSD, SDNN and SDNN Index. Data from 17 patients were analyzed and compared between baseline and FD and among five sessions. The SI was found to be the most sensitive and robust HRV parameter in detecting the ANS response to RD. Out of nine parasympathetic parameters, only the SDNN and SDNN Index were sensitive enough to detect the parasympathetic modulation to RD during the first visit. The frequency-domain parameters did not show any change in response to RD. It was also observed that the repetitive RD in IBS patients resulted in a decreased autonomic response due to habituation because the amount of change in the HRV parameters was the highest during the first visit but diminished during subsequent visits. In conclusion, the SI and SDNN/SDNN Index are most sensitive at assessing the autonomic response to rectal distention. The autonomic response to rectal distention diminishes in repetitive sessions, demonstrating the necessity of randomization for repetitive tests. [ABSTRACT FROM AUTHOR]

Background: Frequent observation of abnormal manometric patterns consistent with dyssynergia in healthy volunteers has warranted the need for reassessment of the current methods to enhance the diagnostic value of anorectal manometry in functional defecatory disorders. Whether rectal distention at simulated evacuation will affect anorectal pressure profile and increase rectoanal gradient is not known. Methods: One hundred and eight consecutive patients with chronic constipation, 93 females, median age 53 years (interquartile range: 40–65), were studied. Simulated evacuation was performed firstly with empty balloon and subsequently after balloon distention to 50 and 100 ml. Anorectal pressures were compared. We also performed subgroup analysis in relation to outcome of balloon expulsion test (BET). In addition, we studied the effect of rectal distension on the rectoanal pressure gradient with respect to rectal sensory function. Results: Rectal balloon distension at simulated evacuation improved rectoanal gradient and decreased the rate of dyssynergia during high-resolution anorectal manometry. In subgroup analysis, the increase in rectoanal gradient and correction of dyssynergia with rectal distension was limited to the patients who had normal BET and normal rectal sensory function. Rate of anal relaxation, residual anal pressures, and rectoanal gradient were significantly different between patients with and without normal BET at 50 ml of rectal distension. Rectoanal gradient recorded only after rectal distension, along with BMI and maximum tolerable volumes, could predict BET results independently in patients with chronic constipation. Conclusions: Rectal distension during simulated evacuation will affect the anorectal pressure profile. Increase in rectoanal gradient and correction of dyssynergia was only significant in patients with normal rectal sensory function and normal BET. [ABSTRACT FROM AUTHOR]

Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N = 100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in 2 widely used pain models for the visceral and somatic modality. Salivary cortisol was increased in the hydrocortisone group (time × group: P < 0.001). For the visceral modality, assessed using pressure-controlled rectal distensions, hydrocortisone decreased the pain threshold from before to after treatment (time × group: P = 0.011), an effect primarily driven by women (time × sex: P = 0.027). For the somatic modality, cutaneous heat pain thresholds remained unaffected by hydrocortisone. Hydrocortisone did not alter perceived pain intensity or unpleasantness of either modality. Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time × modality: P = 0.026), an effect that was significantly reduced by hydrocortisone compared with placebo (time × group: P = 0.028). This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain. [ABSTRACT FROM AUTHOR]

Background and purpose Late anorectal toxicity influences quality of life after external beam radiotherapy (EBRT) for prostate cancer. A daily inserted endorectal balloon (ERB) during EBRT aims to reduce anorectal toxicity. Our goal is to objectify anorectal function over time after prostate intensity-modulated radiotherapy (IMRT) with ERB. Material and methods Sixty men, irradiated with IMRT and an ERB, underwent barostat measurements and anorectal manometry prior to EBRT and 6 months, one year and 2 years after radiotherapy. Primary outcome measures were rectal distensibility and rectal sensibility in response to stepwise isobaric distensions and anal pressures. Results Forty-eight men completed all measurements. EBRT reduced maximal rectal capacity 2 years after EBRT (250 ± 10 mL vs. 211 ± 10 mL; p <  0.001), area under the pressure–volume curve (2878 ± 270 mL mmHg vs. 2521 ± 305 mL mmHg; p  = 0.043) and rectal compliance (NS). Sensory pressure thresholds for first sense and first urge (both p <  0.01) increased. Anal maximum pressure diminished after IMRT ( p  = 0.006). Conclusions Rectal capacity and sensory function are increasingly affected over time after radiotherapy. There is an indication that these reductions are affected less with IMRT + ERB compared to conventional radiation techniques. [ABSTRACT FROM AUTHOR]

This functional magnetic resonance imaging study addressed similarities and differences in behavioral and neural responses to experimental visceral compared with somatic pain stimuli and explored the contribution of fear of pain to differences between pain modalities. In N = 22 healthy women, we assessed blood oxygen level-dependent responses to rectal distensions and cutaneous heat stimuli matched for perceived pain intensity. Fear of pain and pain unpleasantness were assessed before and after scanning. Visceral pain was more fear evoking and more unpleasant, and trial-by-trial intensity ratings failed to habituate across trials (all interactions modality × time: P < 0.01). Differences in fear of pain and pain intensity independently contributed to greater visceral pain unpleasantness (combined regression model: R(2) = 0.59). We observed joint neural activations in somatosensory cortex and frontoparietal attention network (conjunction analysis: all pFWE <0.05), but distensions induced greater activation in somatosensory cortex, dorsal and ventral anterior insula, dorsal anterior and midcingulate cortices, and brainstem, whereas cutaneous heat pain led to enhanced activation in posterior insula and hippocampus (all pFWE <0.05). Fear of visceral pain correlated with prefrontal activation, but did not consistently contribute to neural differences between modalities. These findings in healthy women support marked differences between phasic pain induced by rectal distensions vs cutaneous heat, likely reflecting the higher salience of visceral pain. More studies with clinically relevant pain models are needed to discern the role of fear in normal interindividual differences in the response to different types of pain and as a putative risk factor in the transition from acute to chronic pain. [ABSTRACT FROM AUTHOR]

There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P <0.001), supporting treatment information effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P <0.05): Positive information reduced urgency (P = 0.025), while negative information increased urgency (P = 0.026) only in stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of rectal distension on the quality of anatomical and functional prostate multiparametric (mp) MRI.Materials and Methods: Multiparametric (mp) 3T-MRI images of 173 patients were independently evaluated by two radiologists in this retrospective study. Planimetry rectal volumes were derived and a subjective assessment of rectal distension was made using a 5-point Likert scale (1=no stool/gas, 5=large amount of stool/gas). Image quality of diffusion-weighted imaging (DWI) was evaluated using a 5-point Likert scale. DWI was further scored for distortion and artefact. T2W images were evaluated for image sharpness and the presence of motion artefact. The stability of the dynamic contrast-enhancement acquisition was assessed by recording the number of corrupt data points during the wash-out phase.Results: There was a strong correlation between subjective scoring of rectal loading and objectively measured rectal volume (r=0.82), p<0.001. A significant correlation was shown between increased rectal distension and both reduced DW image quality (r=-0.628, p<0.001), and increased DW image distortion (r=0.814, p<0.001). There was also a significant trend for rectal distension to increase artefact at DWI (r=0.154, p=0.042). Increased rectal distension led to increased motion artefact on T2 (p=0.0096), but did not have a significant effect on T2-sharpness (p=0.0638). There was no relationship between rectal distension and DCE image quality (p=0.693). 63 patients underwent lesion-targeted biopsy post MRI, there was a trend to higher positive predictive values in patients with minor rectal distension (34/38, 89.5%) compared to those with moderate/marked distension (18/25, 72%), p=0.09.Conclusion: Rectal distension has a significant negative effect on the quality of both T2W and DW images. Consideration should therefore be given to bowel preparation prior to prostate mpMRI to optimise image quality. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control. Findings: The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three-dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information. Conclusions: In this cohort of predominately high-risk localised prostate cancer, rectal distension had no significant impact on PSA relapse. We suggest that regular imaging during radiotherapy negates the risk caused by rectal distension on local treatment failure. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rectal distension (RD) is known to induce intestinal dysmotility. Few studies were performed to compare effects of RD, colon distension (CD) and duodenal distension (DD) on small bowel motility. This study aimed to investigate effects and underlying mechanisms of distensions in these regions on intestinal motility and slow waves. Eight dogs chronically implanted with a duodenal fistula, a proximal colon fistula, and intestinal serosal electrodes were studied in six sessions: control, RD, CD, DD, RD + guanethidine, and CD + guanethidine. Postprandial intestinal contractions and slow waves were recorded for the assessment of intestinal motility. The electrocardiogram was recorded for the assessment of autonomic functions. (1) Isobaric RD and CD suppressed intestinal contractions (contractile index: 6.0 ± 0.4 with RD vs. 9.9 ± 0.9 at baseline, P = 0.001, 5.3 ± 0.2 with CD vs. 7.7 ± 0.8 at baseline, P = 0.008). Guanethidine at 3 mg/kg iv was able to partially block the effects. (2) RD and CD reduced the percentage of normal intestinal slow waves from 92.1 ± 2.8 to 64.2 ± 3.4 % ( P < 0.001) and from 90 ± 2.7 to 69.2 ± 3.7 % ( P = 0.01), respectively. Guanethidine could eliminate these inhibitory effects. (3) DD did not induce any changes in small intestinal contractions and slow waves ( P > 0.05). (4) The spectral analysis of the heart rate variability showed that both RD and CD increased sympathetic activity (LF) and reduced vagal activity (HF) ( P < 0.05). Isobaric RD and CD could inhibit postprandial intestinal motility and impair intestinal slow waves, which were mediated via the sympathetic pathway. However, DD at a site proximal to the measurement site did not seem to impair small intestinal contractions or slow waves. [ABSTRACT FROM AUTHOR]

Despite the clinical relevance of nocebo effects, few studies have addressed their underlying neural mechanisms in clinically-relevant pain models. We aimed to address the contribution of nocebo effects and their underlying neural circuitry to central pain amplification in visceral pain, as it may develop over repeated painful experiences due to negative pain-related expectations. Healthy volunteers received verbal suggestions of pain sensitization (nocebo group, N = 28) or neutral instructions (control group, N = 16). fMRI was used to investigate changes in neural responses during cued pain anticipation and painful rectal distensions delivered in successive fMRI sessions. Pain intensity was rated trial-by-trial, and expected pain intensity, state anxiety and tension were assessed prior to each session. Behavioral analyses demonstrated significantly greater increases in both expected and perceived pain in the nocebo group. The fMRI analysis performed on nocebo-responders only (N = 14) revealed that these behavioral changes were associated with increased activation within the secondary somatosensory cortex and amygdala during pain anticipation and within the thalamus, insula and amygdala during painful stimulation when compared to controls. A subsequent psycho-physiological interaction analysis of the pain phase showed increased functional connectivity between the anterior insula, which was set-up as seed region based on group results, and midcingulate cortex as a function of negative expectations. These findings support that negative pain-related expectations can play a crucial role in pain amplification of visceral pain, which is mediated, at least in part, by a neural up-regulation of pain-associated areas and their connectivity. These findings may have implications for the pathophysiology and treatment of chronic abdominal pain. [ABSTRACT FROM AUTHOR]

Background Altered serotonergic (5- HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome ( IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5- HT, 5-hydroxytryptophan (5- HTP), on systemic 5- HT metabolites and visceral perception and to assess potential differential responses between IBS and controls. Methods 15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5- HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma. Key Results 5- HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5- HTP conditions. 5- HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5- HTP significantly increased plasma 5- HTP levels ( p < 0.001), did not affect 5- HT levels ( p > 0.05), while levels of the main metabolite of 5- HT, 5-hydroxyindoleacetic acid, increased significantly ( p < 0.05) in both groups. The magnitude of these changes observed in 5- HT metabolites was significantly greater in IBS patients. Conclusions & Inferences Oral administration of 5- HTP induced significant alterations in systemic 5- HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5- HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5- HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients. [ABSTRACT FROM AUTHOR]

Experiments on conscious dogs addressed the effects of blockade of type 3 serotonin receptors on visceromotor reactions and changes in heart rate (HR) initiated by nociceptive distension of the rectum. Distension of the rectal walls with pressures of 20-60 mmHg were found not to produce significant changes in the electromyographic activity of the abdominal muscles or HR. Distension of the intestine with a pressure of 80 mmHg and greater produced marked visceromotor reactions (contractions of the abdominal muscles) and increases in HR (tachycardia), which are regarded as markers for the occurrence of pain sensations. Use of these indicators allowed the first demonstration in conscious dogs of the dose-dependent antinociceptive effect of blockade of 5-HT receptors with granisetron. Administration of granisetron at doses of 0.25, 0.5, and 1.0 mg/kg was accompanied by prolonged (at least 90 min) decreases in visceromotor reactions to nociceptive rectal distension by 33.6 ± 9.2%, 58.0 ± 8.6%, and 76.7 ± 5.5% of baseline, respectively. In turn, the inhibitory effect of granisetron on tachycardia induced by painful rectal stimulation was seen only immediately after administration. Thus, studies on conscious dogs demonstrated the antinociceptive effect of granisetron in relation to abdominal pain, which may be relevant in the development of pharmacological agents to treat pain in patients with irritable bowel syndrome. [ABSTRACT FROM AUTHOR]

The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3 T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model (‘ LF-HRV model ’). The impact of ANS activity was analyzed by comparing the fMRI signal in the ‘ standard model ’ and in the ‘ LF-HRV model ’ across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Background: Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. Aim: The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Methods: Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Results: Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores ( r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated ( r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits ( r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. Conclusions: VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm. [ABSTRACT FROM AUTHOR]

Abstract: Regional changes in brain structure have been reported in patients with altered visceral sensitivity and chronic abdominal pain, such as in irritable bowel syndrome. It remains unknown whether structural brain changes are associated with visceral sensitivity. Therefore, we present the first study in healthy individuals to address whether interindividual variations in gray matter volume (GMV) in pain-relevant regions correlate with visceral sensitivity. In 92 healthy young adults (52 female), we assessed rectal sensory and pain thresholds and performed voxel-based morphometry (VBM) to compute linear regression models with visceral sensory and pain thresholds, respectively, as independent variable and GMV in a priori-defined regions of interest (ROIs) as dependent variable. All results were familywise error (FWE) corrected at a level of P FWE <.05 and covaried for age. The mean (±SEM) rectal thresholds were 14.78±0.46mm Hg for first sensation and 33.97±1.13mm Hg for pain, without evidence of sex differences. Lower rectal sensory threshold (ie, increased sensitivity) correlated significantly with reduced GMV in the thalamus, insula, posterior cingulate cortex, ventrolateral and orbitofrontal prefrontal cortices, amygdala, and basal ganglia (all P FWE <.05). Lower rectal pain threshold was associated with reduced GMV in the right thalamus (P FWE =.051). These are the first data supporting that increased visceral sensitivity correlates with decreased gray matter volume in pain-relevant brain regions. These findings support that alterations in brain morphology not only occur in clinical pain conditions but also occur according to normal interindividual variations in visceral sensitivity. [Copyright &y& Elsevier]

Abstract: To elucidate placebo and nocebo effects in visceral pain, we conducted a functional magnetic resonance imaging (fMRI) study to analyze effects of positive and negative treatment expectations in a rectal pain model. In 36 healthy volunteers, painful rectal distensions were delivered after intravenous application of an inert substance combined with either positive instructions of pain relief (placebo group) or negative instructions of pain increase (nocebo group), each compared to neutral instructions. Neural activation during cued-pain anticipation and pain was analyzed along with expected and perceived pain intensity. Expected and perceived pain intensity were significantly increased in the nocebo group and significantly decreased in the placebo group. In the placebo group, positive expectations significantly reduced activation of the somatosensory cortex during anticipation and of the insula, somatosensory cortex, and amygdala during pain delivery when compared to neutral expectations. Within the nocebo group, negative expectations led to significantly increased insula activation during painful stimulation. Direct group contrasts during expectation modulation revealed significantly increased distension-induced activation within the somatosensory cortex in the nocebo group. In conclusion, the experience and neural processing of visceral pain can be increased or decreased by drug-specific expectations. This first brain imaging study on nocebo effects in visceral pain has implications for the pathophysiology and treatment of patients with chronic abdominal complaints such as irritable bowel syndrome. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Purpose: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades ≥2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm3, 5.6 cm2, and 53.3 cm3, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades ≥2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is independent of rectal volume/distension while maintaining very low rates of chronic GI toxicity. [Copyright &y& Elsevier]

Abstract: This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level–dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain. [Copyright &y& Elsevier]

Abstract: Aims: It has been suggested that large rectal filling is associated with an increased risk of prostate motion in radiotherapy. The aim of the present study was to determine if there is a correlation between rectal distension on planning computed tomography and the intrafraction and interfraction stability of the prostate gland during a course of radical radiotherapy for prostate cancer if a protocol was used to rescan patients with excessive rectal diameter during planning. Materials and methods: The computed tomography planning scans of 89 patients with adenocarcinoma of the prostate treated with conformal radiotherapy were reviewed. All patients had three gold seed fiducial markers implanted into the prostate before planning computed tomography. About one in five patients had repeat computed tomography because their rectum was judged to be too large at the time of the first planning computed tomography. Rectal distension was assessed on planning computed tomography using outlines following European Organization for Research and Treatment of Cancer guidelines by measuring the rectal volume, the average cross-sectional area and the mean anterior–posterior diameter of the rectum. Daily kV images were obtained before and after treatment delivery to determine positional matching of the fiducial markers in the superior–inferior, anterior–posterior and right–left dimensions. Results: In total, 2860 pre- and post-treatment daily kV image pairs were obtained of 89 patients (average 32.1 image pairs per patient). The median rectal cross-sectional area was 7.3cm2 (range 2.8–17.1), the median rectal volume was 54.8cm3 (range 20.9–128.2), and the median anterior–posterior rectal diameter was 3.03cm (range 1.58–8.30). Unifactor linear regression models showed no statistically significant relationship between intra- and interfraction prostate stability and rectal volume on planning computed tomography. Conclusions: No statistically significant relationship between rectal distension on planning computed tomography and the intra- and interfraction stability of the prostate gland was identified if patients with a large rectal volume were rescanned for planning. [Copyright &y& Elsevier]

Autonomic nervous system dysfunction has been implicated in the pathophysiology of irritable bowel syndrome (IBS). This study characterized the autonomic response to rectal distension in IBS using baroreceptor sensitivity (BRS), a measure of autonomic function. Rectal bag pressure, discomfort, pain, ECG, blood pressure and BRS were continuously measured before, during and after rectal distension in 98 healthy volunteers (34 ± 12 years old, 52 females) and 39 IBS patients (39 ± 11 years old, 35 females). In comparison with the healthy volunteers, IBS patients experienced significantly more discomfort (69 ± 2.2% vs 56 ± 3.6%; P < 0.05), but not pain (9 ± 1.4% vs 6 ± 2.4%; ns) with rectal distension despite similar distension pressures (51 ± 1.4 vs 54 ± 2.4 mmHg; ns) and volumes (394 ± 10.9 vs 398 ± 21.5 mL; ns). With rectal distension, heart rate increased in both healthy volunteers (66 ± 1 to 71 ± 1 bpm; P < 0.05) and IBS patients (66 ± 2 to 74 ± 3 bpm; P < 0.05). Systolic blood pressure also increased in both healthy volunteers (121 ± 2 to 143 ± 2 mmHg; P < 0.05) and patients (126 ± 3 to 153 ± 4 mmHg (P < 0.05) as did diastolic blood pressure, 66 ± 2 to 80 ± 2 mmHg (P < 0.05), compared with 68 ± 3 to 84 ± 3 mmHg (P < 0.05) in IBS patients. The systolic blood pressure increase observed in IBS patients was greater than that seen in healthy volunteers and remained elevated in the post distension period (139 ± 3 mmHg vs 129 ± 2 mmHg; P < 0.05). IBS patients had lower BRS (7.85 ± 0.4 ms mmHg−1) compared with healthy volunteers (9.4 ± 0.3; P < 0.05) at rest and throughout rectal distension. Greater systolic blood pressure response to rectal distension and associated diminished BRS suggests a compromise of the autonomic nervous system in IBS patients. [ABSTRACT FROM AUTHOR]

Rectal perception facilitates maintenance of continence and defecation. Whether perception is associated with motor changes in anorectum is unclear. We examined sensory and motor responses of the anorectum during rectal distention. Stepwise graded rectal balloon distensions were performed in 23 healthy subjects by placing a six-sensor probe in the anorectum. Manometric changes, rectoanal reflexes, and sensory thresholds were assessed. Studies were repeated in six subjects. All subjects showed rectoanal inhibitory and contractile reflexes, but rectal perception was associated with an anal contractile response (sensorimotor response). In 4 subjects (17 percent) the sensorimotor response first occurred synchronously with a sensation of fullness (Group 1) and in 19 (83 percent) with a desire to defecate (Group 2). Mean balloon volume for inducing the sensorimotor response in Groups 1 and 2 were 80 ± 14 ml and 96 ± 26 ml ( P > 0.05). The onset, amplitude, duration, and area under curve of the response were similar in both groups. At higher volumes of balloon distention, all subjects (n = 23) reported a desire and an urge to defecate. The sensorimotor response associated with an urge to defecate had higher amplitude ( P = 0.01) and higher area under curve ( P = 0.001) compared with that associated with a desire to defecate. Repeat studies showed good reproducibility (intraclass correlation coefficient = 0.9; P < 0.05). A desire to defecate is associated with a unique, consistent, and reproducible anal contractile response: the sensorimotor response. This response could play an integral role in regulating anorectal sensation and function. [ABSTRACT FROM AUTHOR]

Objective. Rectal distension is known to induce numerous upper gastrointestinal symptoms. The aim of this study was to investigate the effects and mechanisms of rectal distension on small intestinal myoelectrical and motor activities in 8 dogs using a pair of intestinal electrodes and an intestinal fistula. Material and methods. Experiment 1 entailed a 30-min baseline recording and a 30-min recording during rectal balloon distension at various volumes (60, 80, 100 and 120 ml) randomly. Experiment 2 comprised three sessions, each including a 30-min baseline recording, a 20-min recording after intravenous infusion of saline, phentolamine (3 mg/kg) or propranolol (3 mg/kg), respectively, and another 30-min recording during rectal balloon distending. Results. 1) Rectal distension resulted in reduced intestinal motility in a dose-dependent manner (r=0.68, p<0.001). 2) The reduction in intestinal motility was significantly diminished when infusions of phentolamine (2.7±1.0 versus 8.4±1.5, p<0.01) or propranolol (3.7±1.4 versus 8.4±1.5, p<0.05) were given, suggesting partial involvement of the alpha- and beta-adrenergic pathways. 3) Rectal distension did not affect the percentage of normal 17-22 cycles/min intestinal slow waves (97.5±2.5 versus 93.0±5.3, p>0.05), or their dominant frequency (17.2±1.2 counts per minute (cpm) versus 17.7±1.0 cpm, p>0.05), or dominant power (-4.8±2.5 versus -8.2±2.9 dB, p>0.05). Conclusions. Rectal distension inhibits postprandial small intestinal motor activity in a distension volume-dependent manner in dogs, and this inhibitory effect is at least partially mediated via the alpha and beta adrenergic pathways and does not involve any alterations in intestinal slow waves. [ABSTRACT FROM AUTHOR]

Summary: Background: The mechanisms of interindividual variations in visceral pain sensitivity remain poorly understood. We characterized the neuroendocrine responses to rectal distensions in healthy individuals with high vs. low rectal pain sensitivity. Methods: Rectal sensory and pain thresholds were determined, and a series of random painful distensions was carried out. Eighteen subjects were stratified into groups with a low rectal pain threshold (“High Sensitivity” group) vs. a high rectal pain threshold (“Low Sensitivity” group) by median split, and were compared with regard to adrenocorticotropic hormone (ACTH) and cortisol, cardiovascular, and emotional responses. Results: Distensions led to an anticipatory stress response, reflected by elevated baseline anxiety, and increased baseline ACTH and cortisol in both groups. In response to distensions, the “Low Sensitivity” group showed significantly greater ACTH and cortisol concentrations analysis of variance (ANOVA time×group for ACTH: p<.05; for cortisol: p<.01), and elevated diastolic blood pressures (BP) (ANOVA group: p<.01) when compared to the “High Sensitivity” group. Conclusions: Painful rectal distensions are associated with a pronounced anticipatory stress response, reflected by elevated anxiety and elevated stress hormones. Individuals with high rectal pain sensitivity differ from those with low pain sensitivity in distension-induced hormonal and blood pressure responses, suggesting that neuroendocrine responses may be relevant to the pathophysiology of visceral hyperalgesia. [Copyright &y& Elsevier]

Abstract: Background and purpose: The aim of the study was to define the effect of different rectum fillings in the planning CT study on the posterior clinical target volume (CTV) displacements (PD) in primary and postoperative radiotherapy (RT) for prostate cancer. Materials and methods: Fifty patients underwent CT scans in supine position with a full bladder and an empty bladder before RT and at several points in time during the treatment. PD were determined depending on the initial rectum volume (RV), average cross-sectional rectal area (CSA), and the rectal diameter at the level of the bladder neck (RD). Results: Posterior CTV motion was not found to be minimal with a particularly small initial rectum filling. Steeply increasing PD resulted for patients with RV>120cm3, CSA>12cm2, and RD>4.5cm. While below these critical values a posterior margin of 6mm/9mm allowed to cover 80%/90% of displacements, 18mm/24mm were needed for patients with larger rectum fillings. No correlation of increasing rectum distension with increasing PD was found at the apex level. PD could not be reduced by voiding the bladder. Conclusions: Defining the posterior margin in prostate RT, the initial rectum distension and the superior–inferior CTV level has to be considered. Patients with large initial rectum fillings have preferentially the need for repeated planning CT scans or image-guided RT. [Copyright &y& Elsevier]

Abstract: Background and purpose: The retrospective planning study for intensity-modulated radiotherapy (IMRT) of prostate cancer evaluated whether proximal rectum and supra-anal rectum/anal canal should be delineated as separated organs-at-risk (OARs) to achieve optimal dose distributions to the anorectal region. Patients and methods: For 10 patients with localized prostate cancer IMRT plans were generated with the rectum and anal canal as separated OARs (Rec-sep) and as one single OAR (Rec-tot). Two different treatment planning systems (TPS) were utilized. Influence on dose distributions to target and OARs was analyzed. Results: Results from both TPS showed significantly increased doses to the distal rectum/anal canal for plans Rec-tot compared with Rec-sep in case of a distended rectum in the planning CT study: doses were increased by up to mean 31% (P=0.02) and 18% (P=0.03), respectively, in both TPS. For the patient with the largest rectum, the maximum dose increase was 61%. No significant differences in doses to target, bladder, femoral head and proximal rectum were seen. Conclusions: For patients with a distended rectum in the planning CT, delineation of separated OARs for proximal rectum and distal rectum/anal canal resulted in superior dose distributions to the anorectal region and therefore, we recommend this as standard procedure for IMRT planning of prostate cancer. [Copyright &y& Elsevier]

Background: Visceral hypersensitivity is a consistent finding in a considerable proportion of patients with irritable bowel syndrome (IBS), and may provide a physiological basis for the development of IBS symptoms. In this study, we aimed to confirm the hypothesis that nitric oxide (NO) is involved in maintaining visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients with documented hypersensitivity to rectal distension underwent a rectal barostat study. The effect of placebo and the specific NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) on resting volume, rectal sensitivity to distension and rectal compliance was evaluated in a double-blind, randomized, cross-over fashion. N G-monomethyl-l-arginine did not alter resting volumes in HV or IBS patients. In HV,l-NMMA did not alter rectal sensory thresholds compared to placebo (45 ± 3 and 46 ± 3 mmHg, respectively). In contrast,l-NMMA significantly increased the threshold for discomfort/pain in IBS patients (placebo: 18 ± 2,l-NMMA: 21 ± 3 mmHg, P < 0.05). Rectal compliance was not affected byl-NMMA. Although NO does not seem to play a major role in normal rectal sensation or tone, we provide evidence that NO may be involved in the pathophysiology of visceral hypersensitivity in IBS. [ABSTRACT FROM AUTHOR]

Abstract: Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2±3.5 post-distension vs. 36.6±3.8 post-speech, p <.05), but anxiety was also elevated at baseline (41.6±3.9 vs. 32±3.2 recovery, p <.01). This anticipatory effect was reflected by elevated baseline cortisol (p <.05) and baseline ACTH (p <.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p <.05) and increased CD16+CD56+ cells (p =.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8±9.4mmHg in response to distension vs. +36.4±6.2mmHg in response to speech for systolic BP, p <.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p <.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia. [Copyright &y& Elsevier]

Earlier studies have documented activation of the cingulate cortex during gut related sensory-motor function. However, topography of the cingulate cortex in relationship to various levels of visceromotor sensory stimuli and gender is not completely elucidated. The aim was to characterize and compare the activation topography of the cingulate cortex in response to 1) subliminal, 2) perceived rectal distensions, and 3) external anal sphincter contraction (EASC) in males and females. We studied 18 healthy volunteers (ages 18-35 yr; 10 women, 8 men) using functional MRI blood-oxygenation-level-dependent technique. We obtained 11 axial slices (voxel vol. 2.5-6.0 × 2.5 × 2.5 mm³) through the cingulate cortex during barostat-controlled subliminal, liminal, and supraliminal nonpainful rectal distensions as well as EASC. Overall, for viscerosensation, the anterior cingulate cortex exhibited significantly more numbers of activated cortical voxels for all levels of stimulations compared with the posterior cingulate cortex (P < 0.05). In contrast, during EASC, activity in the posterior cingulate was larger than in the anterior cingulate cortex (P < 0.05). Cingulate activation was similar during EASC in males and females (P = 0.58), whereas there was a gender difference in anterior cingulate activation during liminal and supraliminal stimulations (P < 0.05). In females, viscero-sensory conical activity response was stimulus-intensity dependent. Intestinal viscerosensation and EASC induce different patterns of cingulate cortical activation. There may be gender differences in cingulate cortical activation during viscerosensation. In contrast to male subjects, females exhibit increased activity in response to liminal nonpainful stimulation compared with subliminal stimulation suggesting differences in cognition-related recruitment. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. Methods and Materials: This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. Results: The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). Conclusions: We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore, an empty rectum is warranted at the time of simulation. These results also emphasize the need for image-guided radiotherapy to improve local control in irradiating prostate cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: A knowledge of the relationships between the rectum and its surrounding structures during distention may improve our understanding of the results of studies assessing rectal sensory-motor responses to distention. This magnetic resonance imaging study was designed to assess the shape of the rectum and the degree of distention at which the surrounding structures are compressed. METHODS: Nine healthy patients underwent magnetic resonance imaging of the rectum under resting conditions and after the inflation of a plastic bag to volumes of 50, 100, 150, 200, and 250 ml. The thickness of the rectovesical space was assessed as a measure of the compression of the perirectal structures, and the perception of sensations were recorded. RESULTS: The shape of the rectum changed from being quasicylindrical at distention volumes of <100 ml to bean- shaped at larger volumes. The thickness of the rectovesical space at a distention volume of 50 ml was the same as when the bag was not inflated, but it progressively decreased until the difference became statistically significant at distention volumes of ⩾200 ml, corresponding to a mean ± standard deviation rectal radius of 2.66 ± 0.37 cm. Statistically significant compression of the rectovesical space was recorded when the sensations of gas, desire to defecate, and urgency were perceived. CONCLUSIONS: The shape of the rectum changes during distention; it significantly compresses the extrarectal structures in the tested range of distention that induces nonpainful sensations. Magnetic resonance imaging is a useful means of assessing the morphologic changes in the rectum during distention. [ABSTRACT FROM AUTHOR]

Patients with slow transit constipation frequently have delayed gastric emptying. In animals rectal distensions inhibit gastrointestinal motility. In healthy volunteers isovolumetric rectal distensions delay upper gut transit. The purpose of this study was to determine the effect of continuous isobaric rectal distension on gastric emptying and oro-cecal transit in young females. Using validated 13C octanoic and lactose-[13C] ureide breath tests gastric half-emptying time and oro-cecal transit time for a meal were measured in 12 volunteers. The tests were repeated in randomized order: during isobaric balloon distension and during sham distension. Isobaric rectal distension was applied using a polyethylene bag connected to a barostat. Intraballoon pressure was kept just below the threshold for the urge sensation. Mean gastric half-emptying time during rectal distension (92.3 ±5.1 min) was significantly higher than during sham distension (78.8 ± 4 min; P = 0.015). Mean oro-cecal transit time during rectal distension (391.3 ±29.1 min) and sham distension (328.8 ± 38.4 min) were not significantly different. In conclusion, these findings indicate that isobaric rectal distension inhibits gastric emptying, but not small bowel transit in young healthy women. Studies in patients with constipation are indicated. [ABSTRACT FROM AUTHOR]

Presents an index related to pharmacology published in the June 15, 2003 issue of the journal 'Alimentary Pharmacology & Therapeutics.'

Hormonal cycling may be related to a higher incidence of pain syndrome in female. As tachykinins are pivotal in stress-induced colonic dysfunction, we investigated whether ovarian steroids influence stress-induced visceral hypersensitivity to rectal distension (RD) in female rats and further, whether this influence involves NK1 receptors. Female Wistar rats, either intact or ovariectomized (OVX), were equipped for abdominal muscle electromyography and submitted to 2-h partial restraint stress (PRS) or sham-PRS. First, the effect of PRS was evaluated in intact rats. Second, abdominal response to RD was recorded in OVX rats treated with either, progesterone, 17β-estradiol, 17β-estradiol-plus-progesterone, or vehicle, in both basal and PRS conditions. Third, the NK1 receptor-antagonist, SR140333, was tested in PRS-intact and PRS-OVX rats under 17β-estradiol or 17β-estradiol-plus-progesterone treatment. PRS induced visceral hypersensitivity to RD and this effect was prevented by ovariectomy. OVX rats treated with 17β-estradiol or 17β-estradiol-plus-progesterone, but not progesterone alone, exhibited visceral hypersensitivity after PRS similar to that of intact rats. Both stress-induced visceral hypersensitivity in intact rats and the hormonally-restored visceral hyper-responsiveness of OVX rats were antagonized by SR140333. It is concluded, therefore, that stress-induced visceral hypersensitivity in female rats is estrogens-dependent and mediated through NK1 receptor activation. [Copyright &y& Elsevier]

Abstract It has been suggested that serotonin (5-hydroxytryptamine) type-4 (5-HT 4 ) receptors modulate the sensitivity of intrinsic afferents of the intestinal mucosa. We studied the involvement of 5-HT 4 receptors in the modulation of extrinsic afferent sensitivity of the intestinal wall. During distension ramps, mechanoreceptive rectal afferents in sacral dorsal roots were examined in decerebrate anaesthesia-free cats using the selective 5-HT 4 receptor partial agonist, tegaserod (HTF 919), and the 5-HT 4 receptor antagonist, SB 203186. The static discharge rate of the afferents evoked by rectal distension decreased after intravenous (i.v.) administration of tegaserod at intraluminal pressures above 30 mmHg, with the most effective reduction occurring at 50 mmHg. The effect was dose-dependent, with maximal reduction occurring at 1.2 mg kg -1 bodyweight, and could be partly reversed by i.v. administration of SB 203186. Tegaserod did not alter the pressure–volume relationship (compliance) of the rectum. It is tentatively concluded that 5-HT 4 receptor activation has an inhibitory effect on intramural mechanoreceptors in the cat's rectum. Our results are in line with the observation that tegaserod relieves the sensory symptoms of patients suffering from irritable bowel syndrome. [ABSTRACT FROM AUTHOR]

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. Rectal distension enhanced maximum gallbladder emptying from 66 ± 7% to 78 ± 5% (P < 0·05). Distension tended to increase integrated plasma PYY from 77 ± 30 pM min to 128 ± 40 pM min in the first hour after the meal (P = 0·08) and it suppressed integrated plasma PP from 1133 ± 248 pM min to 269 ± 284 pM min in the second hour (P < 0·05). Integrated plasma CCK concentrations were not significantly affected. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients. [ABSTRACT FROM AUTHOR]

The adequate stimulus that is specific for both rectal mechanoreceptor excitation and rectal perception is still undefined. Using a visual analogue scale, healthy male volunteer subjects rated the intensity of the non-noxious ‘pressure’ sensation evoked by slow balloon-induced distensions of the rectum. In a parallel study, the responses of spinal afferents originating from intramural mechanoreceptors of the rectum to the same stimulus were recorded in decerebrate cats. Both receptor activity and sensation intensity were linearly related to the diameter of the rectum, which is in turn a linear function of the tangential length of the rectal wall. In contrast, both saturated when expressed as a function of intrarectal pressure or rectal wall tension. It is concluded that the perception associated with rectal distensions in the non-noxious range is mediated by intramural mechanoreceptors that linearly encode tangential wall length, and that the underlying information is linearly transmitted throughout the CNS. [ABSTRACT FROM AUTHOR]