Assessment of rectal afferent neuronal function and brain activity in patients with constipation and rectal hyposensitivity

Background Blunted rectal sensation (rectal hyposensitivity: RH) is present in almost one‐quarter of patients with chronic constipation. The mechanisms of its development are not fully understood, but in a proportion, afferent dysfunction is likely. To determine if, in patients with RH, alteration of rectal sensory pathways exists, rectal evoked potentials (EPs) and inverse modeling of cortical dipoles were examined. Methods Rectal EPs (64 channels) were recorded in 13 patients with constipation and RH (elevated thresholds to balloon distension) and 11 healthy controls, in response to electrical stimulation of the rectum at 10 cm from the anal verge using a bipolar stimulating electrode. Stimuli were delivered at pain threshold. Evoked potential peak latencies and amplitudes were analyzed, and inverse modeling was performed on traces obtained to determine the location of cortical generators. Key Results Pain threshold was higher in patients than controls [median 59 (range 23–80) mA vs 24 (10–55) mA; P = 0.007]. Median latency to the first negative peak was 142 (±24) ms in subjects compared with 116 (±15) ms in controls (P = 0.004). There was no difference in topographic analysis of EPs or location of cortical activity demonstrated by inverse modeling between groups. Conclusions & Inferences This study is the first showing objective evidence of alteration in the rectal afferent pathway of individuals with RH and constipation. Prolonged latencies suggest a primary defect in sensory neuronal function, while cerebral processing of visceral sensory information appears normal.     

Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contraction

Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance.     

Rectal hyposensitivity is uncommon and unlikely to be the central cause of obstructed defecation in patients with high‐grade internal rectal prolapse

Background There are several causes of obstructed defecation one of which is thought to be internal rectal prolapse. Operations directed at internal prolapse, such as laparoscopic ventral rectopexy, may improve obstructed defecation symptoms significantly. It is not clear whether the obstructed defecation with internal prolapse is a mechanical phenomenon or whether it results changes in rectal sensitivity. This study aimed to evaluate rectal sensory function in patients with obstructed defecation and high‐grade internal rectal prolapse. Methods This study represents a retrospective review of a prospectively collected database of patients attending a tertiary referral pelvic floor unit. Patients with high‐grade (recto‐anal) intussusception formed the basis of this study. Rectal sensory function was determined by intrarectal balloon inflation. Three parameters (sensory threshold, urge to defecate and maximum tolerated volumes) were recorded. Abnormal sensitivity was defined as partial (one or two parameters abnormal) or total (all three abnormal). Key Results Four hundred and eight patients with high‐grade internal rectal prolapse both with and without obstructed defecation symptoms were studied. Two hundred and forty one (59%) had normal sensation. Eighteen (4%) had total hyposensitivity and three (1%) total hypersensitivity. A further 96 (24%) had partial hyposensitivity whilst 50 (12%) had partial hypersensitivity. Neither hypersensitivity nor hyposensitivity differed between patients with and without symptoms of obstructed defecation. Conclusions & Inferences Rectal hyposensitivity is relatively uncommon in patients with high‐grade internal rectal prolapse and obstructed defecation. Internal rectal prolapse may cause obstructed defecation through a mechanical process. It does not appear that rectal hyposensitivity plays a significant part in the pathological process.     

Anorectal function in patients with collagenous colitis in active and clinically quiescent phase,in comparison with healthy controls

Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re‐assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions & Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.     

Rectal hyposensitivity: pathophysiological mechanisms

Abstract Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. It may occur due to afferent nerve dysfunction and/or secondary to abnormal structural or biomechanical properties of the rectum. The aim of this study was to determine the contribution of these underlying pathophysiological mechanisms by systematically evaluating rectal diameter, compliance and afferent nerve sensitivity in patients with RH, using methodology employed in clinical practice. The study population comprised 45 (33 women; median age 48, range 25–72 years) constipated patients (Rome II criteria) with RH and 20 with normal rectal sensitivity on balloon distension and 20 healthy volunteers. Rectal diameter was measured at minimum distending pressure during isobaric distension under fluoroscopic screening. Rectal compliance was assessed during phasic isobaric distension by measuring the slope of the pressure–volume curve. Electrical stimulation of the rectal mucosa was employed to determine afferent nerve function. Values were compared to normal ranges established in healthy volunteers. The upper limits of normal for rectal diameter, compliance and electrosensitivity were 6.3 cm, 17.9 mL mmHg^?1 and 21.3 mA respectively. Among patients with RH, rectal diameter, but not compliance, was increased above the normal range (megarectum) in seven patients (16%), two of whom had elevated electrosensitivity thresholds. Rectal diameter and compliance were elevated in 23 patients (51%), nine of whom had elevated electrosensitivity thresholds. The remaining 15 patients (33%) with RH had normal rectal compliance and diameter, all of whom had elevated electrosensitivity thresholds. Two‐third of the patients with RH on simple balloon distension have elevated rectal compliance and/or diameter, suggesting that impaired perception of rectal distension is due to inadequate stimulation of the rectal afferent pathway. However, a proportion of such patients also appear to have impaired nerve function. In the remaining one‐third of the patients, rectal diameter and compliance are normal, while electrosensitivity thresholds are elevated, suggestive of true impaired afferent nerve function. Identification of these subgroups of patients with RH may have implications regarding their management.     

Influence of continuous isobaric rectal distension on gastric emptying and small bowel transit in young healthy women

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.     

Disturbances of ano-rectal function in multiple sclerosis

Thirty patients with multiple sclerosis (MS) [18 men and 12 women, mean age 40 years (range 22–50), disease duration 12 years (range 0.5–34), Kurtzke's Expanded Disability Status Score 6.0 (range 4.0–7.5)] were interviewed about bowel symptoms and studied using ano-rectal manometry. The results were compared with findings in healthy controls. Twenty-eight had bowel symptoms: 8 constipation, 10 constipation and infrequent faecal urgency, 4 infrequent faecal incontinence and 6 frequent faecal incontinence. Anal sphincter pressure at rest was significantly reduced in MS patients 69 (SD 17) cm H₂O, compared with 92 (SD 15) cm H₂O in controls, and the external sphincter contraction force was also significantly reduced. Rectal sensation and rectal compliance were reduced and the ano-rectal inhibition reflex (defaecation reflex) required a higher rectal pressure to be elicited in the patients. Upon rectal filling, an early external sphincter excitation was seen. The presence of faecal incontinence correlated strongly with reduced rectal sensation. The findings suggest that faecal incontinence can at least partly be explained by low anal sphincter pressure and poor rectal sensation. The findings of early sphincter excitation and increased threshold of ano-rectal inhibition reflex may be an important pathophysiological factor for constipation in MS patients.     

Effect of acute acoustic stress on anorectal function sensation in healthy human.

Little is known about the effects of acute acoustic stress on anorectal function. To determine the effects of acute acoustic stress on anorectal function and sensation in healthy volunteers. Ten healthy volunteers (7 M, 3 F, mean age 34 +/- 3 years) underwent anorectal manometry, testing of rectal compliance and sensation using a barostat with and without acute noise stress on separate days. Rectal perception was assessed using an ascending method of limits protocol and a 5-point Likert scale. Arousal and anxiety status were evaluated using a visual analogue scale. Acoustic stress significantly increased anxiety score (P < 0.05). Rectal compliance was significantly decreased with acoustic stress compared with control P (P < 0.000001). In addition, less intraballoon volume was needed to induce the sensation of severe urgency with acoustic stress (P < 0.05). Acoustic stress had no effect on hemodynamic parameters, anal sphincter pressure, threshold for first sensation, sensation of stool, or pain. Acute acoustic stimulation increased anxiety scores, decreased rectal compliance, and enhanced perception of severe urgency to balloon distention but did not affect anal sphincter pressure in healthy volunteers. These results may offer insight into the pathogenesis of stress-in-induced diarrhoea and faecal urgency.     

A bi‐directional assessment of the human brain‐anorectal axis

Background Brain‐gut dysfunction has been implicated in gastrointestinal disorders but a comprehensive test of brain‐gut axis is lacking. We developed and tested a novel method for assessing both afferent anorectal‐brain function using cortical evoked potentials (CEP), and efferent brain‐anorectal function using motor evoked potentials (MEP). Methods Cortical evoked potentials was assessed following electrical stimulations of anus and rectum with bipolar electrodes in 26 healthy subjects. Anorectal MEPs were recorded following transcranial magnetic stimulation (TMS) over paramedian motor cortices bilaterally. Anal and rectal latencies/amplitudes for CEP and MEP responses and thresholds for first sensation and pain (mA) were analyzed and compared. Reproducibility and interobserver agreement of responses were examined. Key Results Reproducible polyphasic rectal and anal CEPs were recorded in all subjects, without gender differences, and with negative correlation between BMI and CEP amplitude (r ?0.66, P = 0.001). Transcranial magnetic stimulation evoked triphasic rectal and anal MEPs, without gender differences. Reproducibility for CEP and MEP was excellent (CV <10%). The inter‐rater CV for anal and rectal MEPs was excellent (ICC 97–99), although there was inter‐subject variation. Conclusions & Inferences Combined CEP and MEP studies offer a simple, inexpensive and valid method of examining bidirectional brain‐anorectal axes. This comprehensive method could provide mechanistic insights into lower gut disorders.     

Pre-experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions

Abstract  Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se . In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment ( P  = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls ( P  = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation ( P  = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.     

Altered recto-anal motility in irritable bowel syndrome: a clinical physiological study of 80 Mexican patients

Between 1989 and 1991, 347 out-patients suffering from functional bowel disease were studied. Eighty (mean age 33.4 ± 1, range 17–53 years: 75 females) met the established criteria for irritable bowel syndrome. After noting their clinical history, they underwent standard laboratory tests, air contrast barium enema, recto-sigmoidoscopy; rectal sensitivity studies, and recordings of both electrical and mechanical activities of the distal rectum and the internal anal sphincter during 2 h inter digestive and 2 h post-prandial periods. Twenty-one normal subjects served as a control group. In the irritable bowel syndrome, both basal (P = 0.01) as well as post-prandial (P = 0.003) rectal spike amplitudes were higher compared with controls. While there was no significant difference in the induced recto-anal inhibitory reflex, the frequency (P = 0.001), duration (P = 0.007) and amplitude (P = 0.03) of spontaneous anal relaxations were all greater in the patients compared with the control. Patients perceived the rectal sensation and discomfort at significantly lower values than normal subjects (P < 0.01). In summary, irritable bowel syndrome patients showed increased electrical activity of the rectum in response to food and increased frequency, duration, and amplitude of the naturally occurring recto-anal inhibitory reflex, and a sensitive rectum.     

Pathology in Senile Patients with Abnormal Body Sensation

Background : Senile people tend to develop abnormal body sensations such as delusion of parasitosis. To discuss the pathology of senile abnormal body sensation, we studied patients with abnormal body sensation, cenesthopathy, and delusion of parasitosis and investigated their age and gender.
Methods : The subjects were a mix of patients reported in Japan and our patients. They were classified into two groups; Group 1 were those with a condition considered to be a somatoform disorder and Group 2 were those with a delusion of parasitosis and chronic tactile hallucinosis.
Results : Group 1 consisted of 29 patients aged 46.4±9.6 years; the male:female ratio was 1:4.8. Group 2 consisted of 51 patients aged 65.8±9.4 years; the male:female ratio was 1:1.125.
Conclusion : Based on the age tendency characteristics, Group 1 was called the involutional group and Group 2 the senile group. The age and gender distribution in the involutional group (Group 1) may be related mainly to climacteric disorders and suggested some influences of climacteric changes on the appearance of abnormal body sensation. On the other hand, the pathology in the senile group (Group 2) appeared to be associated with senile organic changes in addition to climacteric changes and sensory changes of skin and mucosal area during the involutional period.     

Rapid rate magnetic stimulation of human sacral nerve roots alters excitability within the cortico‐anal pathway

Abstract Sacral nerve root stimulation (SNS) can produce dramatic symptomatic improvement in faecal incontinence (FI). However, the physiological mechanism behind this improvement remains unknown. One hypothesis is that SNS may modulate cortico‐anal pathways and drive compensatory changes within the spinal cord or cerebral cortex that beneficially alter sphincter function. Our aim was to assess whether short‐term experimental SNS can induce changes in the human cortico‐anal pathway. Eight healthy volunteers (mean age 30 years) were studied. Subjects were investigated on three separate occasions and randomized to either active (5 and 15 Hz) or sham rapid‐rate lumbosacral magnetic stimulation (rLSMS). Anal sphincter electromyograms (EMG) were recorded from an anal probe following single‐pulse transcranial magnetic stimulation, at baseline, immediately, 30 and 60 min following rLSMS at either (i) 5 Hz for 15 min, (ii) 15 Hz for 15 min or (iii) sham stimulation for 15 min. In addition, manometry and anal sphincter sensation was measured in a subset of subjects. Interventions were compared to sham using anova . Fifteen hertz rLSMS increased cortico‐anal EMG response amplitude in the 1 h postintervention (F_{4, 28} = 3.2, P = 0.027), without a shift in response latency. This effect was not demonstrated with either 5 Hz or sham stimulation. rLSMS had no short‐term effect on sensation or physiology. Short‐term magnetic stimulation of the sacral nerve roots induces changes in cortico‐anal excitability which is frequency specific. These data support the hypothesis that SNS produces some of its beneficial effect in patients with FI by altering the excitability of the cortico‐anal pathway.     

Abnormal rectal motor physiology in patients with irritable bowel syndrome

A contentious issue is whether irritable bowel syndrome (IBS) patients have abnormal rectal motor physiology. Our aim was to determine whether IBS patients have abnormal rectal responses to low (urge producing) or high (pain producing) distension pressures. The IBS patients and healthy controls underwent five series of isobaric rectal distensions to examine volume-pressure relationships and rectal accommodation: (i) ascending stepwise distensions terminating upon report of moderate pain, (ii) phasic and (iii) tonic distensions at a single low pressure producing a moderate sensation of urge to defecate (iv) phasic and (v) tonic distensions at a single high pressure producing a moderate pain sensation. The IBS patients demonstrated a lower rectal volume-pressure ratio during repetitive single-pressure phasic distensions, and a slower rate of rectal accommodation during low (but not high) pressure tonic distensions. However, dynamic compliance during ascending stepwise distensions and the change in rectal volume during tonic distension were not significantly different from controls. Rectal abnormality was readily demonstrated by determining the volume-pressure ratio using a small number of repetitive single-pressure distensions, supporting the hypothesis that IBS patients have abnormal rectal motor physiology. We propose that a peripheral neuromuscular substrate may contribute to the pathogenesis of IBS.     

Colonic transit time and rectoanal videomanometry in Parkinson's disease

BACKGROUND: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD). OBJECTIVE: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. METHODS: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). RESULTS: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). CONCLUSIONS: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.     

What is the optimum methodology for the clinical measurement of resting anal sphincter pressure?

There are conflicting recommendations from consensus groups with regard to the assessment of resting anal sphincter pressure. Our aims were to evaluate and compare the performance of three recognized techniques for the clinical measurement of resting anal sphincter pressure. METHODS: In each of 54 patients presenting for anorectal manometry, and suffering from constipation or fecal incontinence, three different techniques for assessment of resting anal pressure were undertaken, namely stationary, stationary pull-through and slow pull-through techniques. Resting anal sphincter pressures were compared between groups and between techniques. RESULTS: Mean resting anal sphincter pressure was lower with stationary, compared with stationary pull-through and slow pull-through, techniques (P < or = 0.002). Resting pressure was higher for constipation than incontinence regardless of technique used (P < 0.00001). The techniques were highly correlated with each other (P < 0.0001). The stationary pull-through technique conferred a minor advantage in the discrimination between constipation and incontinence. The stationary technique required significantly less time for completion (P < 0.0001). CONCLUSION: Resting anal sphincter pressure varies according to the specific technique employed, yet each technique is valid. The stationary pull-through technique confers a minor advantage in clinical discrimination of patients, but the stationary technique is more time-efficient. Standardized anal sphincter testing should be established to enable inter-laboratory comparisons.     

Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome

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 NG -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. NG -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 by L-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.     

Sympathetic (electrodermal) activity during repeated maximal rectal distensions in patients with irritable bowel syndrome and constipation

Abstract  Irritable bowel syndrome (IBS) is associated with visceral hypersensitivity, stress and autonomic dysfunction. Sympathetic activity during repeated events indicates excitatory or inhibitory mechanisms such as sensitization or habituation. We investigated skin conductance (SC) during repetitive rectal distensions at maximal tolerable pressure in patients with IBS and chronic constipation. Twenty-seven IBS patients, 13 constipation patients and 18 controls underwent two sets of isobaric rectal distensions. First, maximal tolerable distension was determined and then it was repeated five times. Skin conductance was measured continuously. Subjective symptom assessment remained steady in all groups. The baseline values of SC were higher in IBS patients than in patients with constipation and significantly lower in constipation patients than in controls. The maximal SC response to repetitive maximal distensions was higher in IBS patients compared with constipation patients. The amplitude of the initial SC response decreased successively with increased number of distensions in patients with IBS and constipation but not in controls. Irritable bowel syndrome and constipation patients habituated to maximal repetitive rectal distensions with decreasing sympathetic activity. Irritable bowel syndrome patients had higher sympathetic reactivity and baseline activity than constipation patients. A lower basal SC in constipation patients compared with controls suggests an inhibition of the sympathetic drive in constipation patients.     

Effects of vaginal hysterectomy on anorectal sensorimotor functions--a prospective study

Background While bowel and bladder dysfunction are recognized consequences of a radical hysterectomy, the effects of a simple hysterectomy on anorectal sensorimotor functions, particularly rectal sensation, vary among studies and the effects on rectal compliance remain unknown. Our aims were to prospectively evaluate anorectal sensorimotor functions before and after a hysterectomy. Methods Anal pressures, rectal compliance, capacity, sensation, and bowel symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal hysterectomy for benign indications in 19 patients. Rectal staircase (0–44 mmHg, 4‐mmHg steps), ramp (0–200 mL at 50, 200 and 600 mL min^?1) and phasic distentions (8, 16, and 24 mmHg above operating pressure) were performed. Key Results Anal resting (63 ± 4 before, 56 ± 4 mmHg after) and squeeze pressures (124 ± 12 before, 124 ± 12 mmHg after), rectal compliance and capacity (285 ± 12 before, 290 ± 11 mL 1 year after), and perception of phasic distentions were not different before vs after a hysterectomy. Sensory thresholds for first sensation and the desire to defecate were also not different, but pressure and volume thresholds for urgency were somewhat greater (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy. Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp distention; this rate effect was greater at 1 year after a hysterectomy, particularly at 100 mL (P = 0.04). Conclusions & Inferences A simple vaginal hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency and increased stiffness during rapid distention) on rectal sensorimotor functions.     

Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients.

Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrate's effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement < 3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre- and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Student's t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (>3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P < 0.01) and the total colon (P < 0.05). During rectal filling, mosapride lessened the first sensation (P < 0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P < 0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.