Rectal distention testing in patients with irritable bowel syndrome: sensitivity,specificity, and predictive values of pain sensory thresholds

BACKGROUND & AIMS: Visceral hypersensitivity was detected in patients with functional gastrointestinal disorders and has been proposed as a biological marker of irritable bowel syndrome (IBS). The purpose of this study was to assess the sensitivity, specificity, and the predictive values of pain thresholds evaluated by rectal distention using an electronic barostat in patients with or without IBS and in control subjects. METHODS: Patients were diagnosed according to Rome II criteria. Rectal sensory thresholds were determined in 164 patients (86 IBS patients, 26 painless constipation, 21 functional dyspepsia, and 31 miscellaneous conditions) and in 25 normal controls. All subjects underwent a series of rectal isobaric distentions using an electronic barostat. The bag was progressively distended from 0 to 48 mm Hg and, in response to distention, subjects reported on discomfort or pain. RESULTS: Pain thresholds were lower in IBS patients (30.4 +/- 6.7 mm Hg) compared with controls (44.5 +/- 5), painless constipated (45.4 +/- 5.3), functional dyspepsia (39.4 +/- 7.8), and miscellaneous patients (43.2 +/- 5.5). At the level of 40 mm Hg, the sensitivity of the rectal barostat to identify IBS patients from normal subjects and non-IBS patients was 95.5% and its specificity was 71.8%. The positive predictive value was 85.4%. The negative predictive value was 90.2%. CONCLUSIONS: Lowered rectal pain threshold is a hallmark of IBS patients. Rectal barostat testing is useful to confirm the diagnosis of IBS and to discriminate IBS from other causes of abdominal pain.     

Sensitivity disturbances in patients with irritable bowel syndrome and fibromyalgia

BACKGROUND: Although visceral hypersensitivity is a common feature among patients with irritable bowel syndrome (IBS), studies on somatic sensitivity have given controversial results. AIM: To assess visceral sensitivity in response to isotonic rectal distensions and somatic sensitivity at different layers of the body wall (skin, subcutis, and muscle) in patients with IBS and fibromyalgia (FM), within and outside the area of abdominal pain referral. MATERIALS AND METHODS: We studied 10 patients with IBS, 5 patients with FM, 9 patients with IBS+FM, and 9 healthy controls. Rectal distensions were performed by increasing tension at 4 g steps up to 64 g or discomfort. Pain thresholds to electrical stimulation were measured within and outside the areas of abdominal pain referral. RESULTS: Patients with IBS and IBS+FM demonstrated rectal hypersensitivity in comparison to controls. The threshold of discomfort was 44 +/- 5 g in IBS and 36 +/- 5 in IBS+FM patients, while patients with FM and healthy controls tolerated all distensions without discomfort. In the areas of pain referral, pain thresholds of all three tissues of the body wall were lower than normal in all patients groups (p < 0.001). In control areas, the pain thresholds were normal in skin, and lower than normal in subcutis and muscle in IBS (p < 0.001). FM and IBS+FM demonstrated somatic hypersensitivity at all sites (p < 0.001 vs healthy). CONCLUSION: Our observations seem to indicate that, although sharing a common hypersensitivity background, multiple mechanisms may modulate perceptual somatic and visceral responses in patients with IBS and FM.     

Impact of coexisting irritable bowel syndrome on symptoms and pathophysiological mechanisms in functional dyspepsia

Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). AIM: The aim of the present study was to investigate whether coexisting IBS is also associated with symptom pattern or pathophysiology in FD. METHODS: In 309 consecutive FD patients (207 women, age 42 +/- 0.8 yr), questionnaires were used to assess the dyspepsia symptom pattern and the Rome II criteria for IBS. The overall symptom severity was calculated adding the severity score (0-3, 0 = absent, 3 = severe) of eight dyspepsia symptoms. All patients underwent Helicobacter pylori testing, gastric barostat to determine sensitivity to distention and accommodation to a meal, and gastric emptying breath test. RESULTS: Fifty-four percent of the patients had FD alone, whereas 46% had FD + IBS. FD + IBS patients were more likely to be female (75%vs 60%, p < 0.01) and to have a greater weight loss (5.4 +/- 0.6 vs 3.5 +/- 0.4 kg, p < 0.05). Coexisting IBS did not increase the risk of having any of the dyspeptic symptoms but the overall symptom severity was significantly higher in FD + IBS (12.4 +/- 0.4 vs 9.8 +/- 0.3, p < 0.01). FD + IBS patients had a lower threshold for first perception (2.9 +/- 0.3 vs 3.8 +/- 0.3 mmHg, p < 0.05) and for discomfort (7.9 +/- 0.4 vs 9.5 +/- 0.5 mmHg, p < 0.05) and a greater prevalence of hypersensitivity to gastric distention (44%vs 28%, p < 0.05). Gastric emptying, accommodation to a meal, and prevalence of H. pylori infection did not differ in the two groups. CONCLUSION: About half of the FD patients fulfill the Rome II criteria for IBS. FD + IBS is more prevalent in female patients and is associated with a higher weight loss, with greater overall symptom severity, and with hypersensitivity to distention.     

Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS): effect of a low-fat intraduodenal infusion

BACKGROUND: Visceral hypersensitivity is common in Irritable Bowel Syndrome (IBS) patients, and symptoms exacerbate postprandially. Yet the effects of nutrients on visceral sensitivity and symptoms in these patients have not been fully explored. AIMS: To evaluate the differences of visceral sensitivity and symptoms in healthy subjects and IBS patients during fasting and intraduodenal lipids infusion. METHODS: Graded rectal distensions at fixed tension levels were performed in 16 IBS patients (8 IBS-C and 8 IBS-D) and 6 healthy subjects before and during intraduodenal lipids infusion at 0.5 kcal/min. Tension levels were increased in 4 gr increments up to 64 gr or discomfort during both conditions. At each step, perception and symptoms were measured by means of a validated questionnaire. RESULTS: In basal conditions, perception thresholds in IBS patients and health were, respectively, 8 +/- 2 gr versus 32 +/- 9 gr (p < 0.001) with no changes during lipids. Intraduodenal lipids infusion significantly lowered threshold of discomfort in IBS patients in comparison to fasting (24 +/- 6 gr vs 34 +/- 4 gr; p < 0.05), while health tolerated all distension without discomfort. No differences of compliance, perception, or discomfort were observed between the two subgroups of patients at each tension step. The predominant symptom elicited in patients with IBS-C was abdominal pain (54%), while patients with IBS-D exhibited urgency (63%, p < 0.005); this pattern was maintained during lipids. CONCLUSIONS: Intraduodenal lipids increase visceral sensitivity in both IBS-C and IBS-D; symptoms specificity in response to rectal distension is maintained in the postprandial period. Lipids may be responsible for the postprandial symptoms exacerbation in IBS.     

Rectal afferent hypersensitivity and compliance in irritable bowel syndrome: differences between diarrhoea-predominant and constipation-predominant subgroups

OBJECTIVES: To evaluate the differences in rectal compliance and sensory thresholds for the urge to defecate and discomfort between irritable bowel syndrome (IBS) subgroups and controls, and to correlate these parameters with rectal symptoms. METHODS: A total of 38 IBS patients [Rome II criteria; 19 diarrhoea-predominant IBS (D-IBS), 16 constipation-predominant IBS (C-IBS), three with alternating diarrhoea and constipation IBS (Alt-IBS)] and 10 controls were studied. A barostat was used to measure rectal compliance and sensory thresholds, in the 'unprepared' rectum. The thresholds for the urge to defecate and discomfort were determined using phasic rectal balloon distension in a double random staircase sequence. RESULTS: D-IBS had significantly lower rectal compliance and threshold for the urge to defecate compared with controls [4 ml/mmHg interquartile range (IQR) 3.99 versus 8.4 ml/mmHg IQR 5.69; P=0.001; 8 mmHg IQR 6 versus 20 mmHg IQR 4; P=0.003]. D-IBS also had significantly lower rectal compliance and threshold for the urge to defecate compared with the C-IBS group (5.8 ml/mmHg IQR 4.61; P=0.027; 16 mmHg IQR 12; P=0.003). The volume at the threshold for discomfort was significantly lower in D-IBS compared with controls (163 ml IQR 99.5 versus 212 ml IQR 147.25; P=0.016). The severity of abdominal pain and rectal symptoms showed a significantly negative correlation with rectal sensory thresholds. CONCLUSION: This study shows that the sensory threshold for the urge to defecate and rectal compliance is significantly lower in D-IBS compared with C-IBS and controls. The consequent inability to tolerate rectal faecal loading may account for the symptoms of the passage of frequent, small-volume stools in D-IBS patients.     

Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome

OBJECTIVE: Abdominal pain is thought to be a hallmark of the irritable bowel syndrome (IBS), although currently used symptom criteria do not differentiate between abdominal pain and discomfort. By focusing on viscerosensory symptoms, we sought to determine: 1) which type of symptoms are most commonly reported by IBS patients, and 2) whether patients who report pain as their most bothersome symptom differ in clinical, psychological, and physiological characteristics. METHODS: A total of 443 consecutive new patient referrals to a tertiary referral center for functional gastrointestinal disorders who met symptom criteria for IBS were given validated, psychometric, health status, and bowel symptom questionnaires containing specific questions regarding the patients' predominant viscerosensory gastrointestinal symptom. Of these patients, 155 (35%) also met criteria for functional dyspepsia. A representative subset of the total IBS patient population (n = 58) underwent evaluation of perceptual responses to controlled rectal distension before and after a noxious sigmoid conditioning stimulus. RESULTS: Viscerosensory symptoms clustered into four groups: 1) abdominal pain, 2) bloating-type discomfort, 3) sensation of incomplete rectal evacuation, and 4) extraabdominal (chest pain or pressure and nausea). A total of 66% of patients reported gas as one of their viscerosensory symptoms, whereas 60% reported abdominal pain as one of their symptoms. Only 29% rated abdominal pain as their most bothersome symptom, whereas bloating-type symptoms were listed by 60% as most bothersome. Although pain predominance did not correlate with the severity of gastrointestinal or psychological symptoms, there was a significant correlation with the development of rectal hypersensitivity in response to the sigmoid conditioning stimulus. CONCLUSIONS: In a tertiary referral population of IBS patients: 1) abdominal pain is reported by only one third of patients as their most bothersome viscerosensory symptoms; and 2) pain-predominance correlates with development of rectal hypersensitivity after a noxious sigmoid stimulus.     

Altered rectal perception in irritable bowel syndrome is associated with symptom severity

BACKGROUND & AIMS: Diverging results exist regarding the connection between altered visceral perception and gastrointestinal (GI) symptoms, as well as the effects of psychological status on visceral sensitivity. We sought to investigate different aspects of rectal perception in irritable bowel syndrome (IBS) and the association with GI and psychological symptoms. METHODS: We included 109 patients with IBS meeting Rome II criteria (77 women; age range, 20-71 years) and 29 healthy controls (21 women; age range, 20-68 years). They underwent rectal balloon distentions determining sensory thresholds for discomfort and pain, the perceived intensity of unpleasantness, and the viscerosomatic referral area. The fifth percentile (thresholds) and 95th percentile (unpleasantness and referral area) in controls were used to define altered perception. Questionnaires were used to assess severity of IBS-related GI symptoms and psychological symptoms. RESULTS: When combining the 3 aspects of perception, 67 patients (61%) had altered rectal perception. These patients, compared with normosensitive patients, more frequently reported moderate or severe pain (73% vs 44%; P < .01), bloating (73% vs 36%; P < .0001), diarrhea (47% vs 21%; P < .01), satiety (39% vs 13%; P < .01), and clinically significant anxiety (31% vs 12%; P < .05). In a multivariate analysis, only pain and bloating remained associated with altered rectal perception. CONCLUSIONS: Altered rectal perception is common in IBS and seems to be one important pathophysiologic factor associated with GI symptom severity in general and pain and bloating in particular. It is not just a reflection of the psychological state of the patient.     

Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls

BACKGROUND: Abnormal visceral mechano-sensory function has been reported in 50% of non-ulcer (functional) dyspepsia patients. However, only a minority of subjects with functional dyspepsia ever seek medical attention. Whether factors promoting health care seeking behaviour explain visceral hypersensitivity is unknown. Decreased rectal thresholds following sigmoid mechanical stimulation have been observed in irritable bowel but this mechanism has not been evaluated in functional dyspepsia. AIMS: To compare visceral mechanosensory function in healthy asymptomatic subjects and non-consulters with chronic unexplained dyspepsia. METHODS: Forty two volunteers were recruited: 10 had a history of chronic or recurrent upper abdominal pain or discomfort as assessed by a standardised questionnaire, and Helicobacter pylori status was determined (ELISA and (13)C urea breath test). Eight H pylori negative, currently asymptomatic dyspeptic subjects who were non-consulters and eight asymptomatic age and sex matched H pylori negative controls were enrolled. With a barostat bag in the proximal part of the stomach, visceral perception thresholds were determined by random tracking. Thereafter, standardised ramp distensions were performed (2 mm Hg increments, duration of each pressure step 30 seconds, maximum pressure 35 mm Hg (or occurrence of pain)) and tracking of sensory thresholds and ramp distension repeated every 30 minutes for a total of two hours. RESULTS: Overall, thresholds for first perception were significantly lower in dyspeptic subjects compared with asymptomatic controls (12.5 (0.6) mm Hg v 17.5 (1.0) mm Hg; p<0.02). After repeated ramp distensions, thresholds for first perception significantly increased by 3.6 (0.7) mm Hg in healthy subjects compared with 0.1 (1.4) mm Hg in subjects with dyspepsia (p<0.05 dyspeptics v controls). CONCLUSIONS: (1) Repeated mechanical stimulation increases visceral sensory thresholds in asymptomatic subjects while thresholds remain unchanged in dyspeptics. (2) Visceral hyperalgesia occurs in dyspeptic subjects who are not health care seekers.     

The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.

BACKGROUND & AIMS: Although widely prescribed, the evidence for the use of antidepressants for the treatment of irritable bowel syndrome (IBS) is limited. In this study, we hypothesized that fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has visceral analgesic properties, leading to increased sensory thresholds during rectal distention and improvement of symptoms, in particular in IBS patients with visceral hypersensitivity. METHODS: Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo. Abdominal pain scores, individual gastrointestinal symptoms, global symptom relief, and psychologic symptoms were assessed before and after the intervention. RESULTS: At baseline, 21 of 40 patients showed hypersensitivity to rectal distention. Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo, either in hypersensitive (19 +/- 3 vs. 22 +/- 2 mm Hg above MDP) or in normosensitive (34 +/- 2 vs. 39 +/- 4 mm Hg above MDP) IBS patients. Overall, 53% of fluoxetine-treated patients and 76% of placebo-treated patients reported significant abdominal pain scores after 6 weeks (not significant). In contrast, in hypersensitive patients only, fluoxetine significantly reduced the number of patients reporting significant abdominal pain. Gastrointestinal symptoms, global symptom relief, and psychologic symptoms were not altered. CONCLUSIONS: Fluoxetine does not change rectal sensitivity in IBS patients. Possible beneficial effects on pain perception need to be confirmed in larger trials.     

Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance

BACKGROUND: Rectal sensory thresholds are lowered in patients with irritable bowel syndrome (IBS), reflecting visceral hyperlagesia, which might be related to subclinical inflammation. AIM: To evaluate the effects of an intraluminal injection of glycerol, a mucosal irritant, on rectal tone and perception of distension in 12 healthy subjects. METHODS: Rectal tone was evaluated with a barostat. First sensation, need to defecate and pain thresholds were evaluated during isobaric phasic distensions, before and 20 and 120 min after injection of 10 ml glycerol in the rectum. RESULTS: Baseline bag volume (97.9 +/- 56.2 ml) significantly decreased 20 min (49.7 +/- 42.2 ml; P= 0.026) and 120 min (66.5 +/- 38.3 ml; P= 0.050) after injection of glycerol, indicating its hypertonic effect. The pressure defining sensory thresholds was decreased significantly 20 min after glycerol injection: first sensation, 14.6 +/- 2.9 versus 18.3 +/- 7.2 mm Hg (P = 0.01); need to defecate, 19.6 +/- 3.7 versus 26.0 +/- 6.9 mm Hg; pain, 23.8 +/- 4.5 versus 35.6 +/- 9.5 mm Hg (P = 0.001). This effect was maintained for 120 min after injection of glycerol. Slopes of the compliance curves did not differ before and after injection of glycerol. CONCLUSIONS: Intraluminal injection of glycerol significantly increases rectal tone and sensitizes healthy volunteers to rectal distension, since they show significantly lower thresholds after glycerol. This could constitute a model of visceral hypersensitivity in healthy volunteers.     

Alteration of the spinal modulation of nociceptive processing in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity has been evidenced in patients with irritable bowel syndrome (IBS) but its mechanisms remain poorly elucidated. We investigated the spinal transmission of nociceptive signals in IBS patients by analysing the effects of rectal distensions on electromyographic recordings of the somatic nociceptive flexion (RIII) reflex, an objective index of spinal nociceptive processes. METHODS: Fourteen IBS and 10 healthy volunteers were included in the study. Slow ramp (40 ml/min) and rapid phasic (900 ml/min, 10, 20, 30, and 40 mm Hg) rectal distensions were randomly performed while the RIII reflex evoked by electrical stimulation of the sural nerve at the ankle was continuously recorded from the ipsilateral biceps femoris. RESULTS: In healthy volunteers, significant progressive inhibition of the RIII reflex was observed during slow ramp distension (61 (13)% of control values) while biphasic effects (facilitation and inhibition) were observed during rapid distensions. In contrast, in IBS patients, the RIII reflex was significantly facilitated during slow ramp distension (139 (15)% of control values) and inhibitions induced by rapid distensions were significantly reduced. Volumes of distension and rectal compliance were similar in both groups. CONCLUSIONS: Our results provide direct evidence that a hyperexcitability of spinal nociceptive processes is present in a large subgroup of IBS patients.     

Visceral perception thresholds after rectal thermal and pressure stimuli in irritable bowel syndrome patients

BACKGROUND AND AIM: Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). The current study sought to compare the characteristics of visceral perception thresholds after rectal thermal and pressure stimuli between IBS patients and healthy subjects. METHODS: A total of 46 patients with IBS were diagnosed using Rome II criteria. Thirteen healthy individuals participated in the study. Rectal visceral perception thresholds were examined in patients with IBS and in normal controls after thermal and pressure stimuli. Subjects were asked to report the sensation type, location, and spread. RESULTS: Compared with healthy subjects, IBS patients demonstrated significantly initially lower perception thresholds and defecation thresholds to rectal thermal and pressure stimuli, particularly in patients with diarrhea-predominant IBS. Ice stimuli on the abdominal wall had varied effects on symptoms in patients with IBS and did not affect perception thresholds. CONCLUSIONS: Visceral perception thresholds were decreased significantly after rectal thermal and pressure stimuli in patients with IBS. Visceral hypersensitivity may be one of the important pathogenic mechanisms in IBS.     

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.     

The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers

BACKGROUND: We have previously shown that the menstrual cycle has no effect on rectal sensitivity of normal healthy women, despite them having looser stools at the time of menses. Patients with irritable bowel syndrome (IBS) often report significant exacerbation of their IBS symptoms with menses, raising the possibility that IBS patients may respond differently to the menstrual cycle. AIM AND METHODS: Rectal responses to balloon distension during days 1-4 (menses), 8-10 (follicular phase), 18-20 (luteal phase), and 24-28 (premenstrual phase) of the menstrual cycle were assessed in 29 female IBS patients (aged 21-44 years), diagnosed by the Rome I criteria. During the course of the study patients completed symptom diaries to assess abdominal pain and bloating (visual analogue scale), and frequency and consistency of bowel habits. In addition, levels of anxiety and depression were assessed using the hospital anxiety and depression questionnaire. RESULTS: Menses was associated with a worsening of abdominal pain and bloating compared with most other phases of the menstrual cycle (p<0.05). Bowel habits also became more frequent (p<0.05) and patients tended to have a lower general well being. Rectal sensitivity increased at menses compared with all other phases of the cycle (p<0.05). There was no associated change in rectal compliance, wall tension, or motility index. Neither was there any difference in resting anal pressure or the distension volumes required to relax the internal anal sphincter during the menstrual cycle. CONCLUSION: These data (1) confirm that IBS symptomatology is exacerbated at menses and (2) show for the first time that in contrast with healthy women, rectal sensitivity changes with the menstrual cycle. These cyclical changes in sensitivity suggest that women with IBS respond differently to fluctuations in their sex hormonal environment or its consequences compared with healthy females.     

Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone

Effects of octreotide (1.25 µg/kg subcutaneously) on colonic tone and visceral perception were evaluated in 10 IBS patients, using a barostat and compared to placebo in a double-blind crossover study. Colonic sensory thresholds were also studied in healthy controls for comparison with IBS patients. Colonic tone was reflected by variations in volume of the barostat balloon. Baseline volume was 117±38 ml and was not modified by placebo (122±40 ml) or octreotide (106±42 ml). After the meal, maximal decrease in balloon volume was 75±4% following placebo (P<0.001) beginning after 9±3 min and lasting 136±17 min. Following octreotide, the maximal decrease was 69±16% (NS vs placebo), after 10±3 min and lasting 140±22 min. In the second part, discomfort and pain thresholds were evaluated during isobaric distensions (4 mm Hg increments, 5-min duration, 5-min interval with return to pressure 0 between each). The pressure inducing discomfort was 21.2±5.9 mm Hg following placebo vs 29.6±6.6 mm Hg following octreotide (P<0.01). The pressure inducing pain was 24.8±7.3 mm Hg following placebo vs 33.2±7.3 mm Hg following octreotide (P<0.01). In healthy subjects, discomfort and pain were induced by colonic distensions at a mean intraballoon pressure of 32.7±5.8 mm Hg and 36.7±3.9 mm Hg, respectively. Compliance curves were not different following placebo and octreotide. Octreotide significantly increases thresholds for visceral perception in IBS patients without modifying compliance during distension nor colonic tone.     

Clinical patterns over time in irritable bowel syndrome: symptom instability and severity variability

OBJECTIVES: The clinical course of irritable bowel syndrome (IBS) remains poorly known. In 209 IBS patients meeting Rome II criteria (137 females and 72 males) we evaluated: (1). changes in frequency and intensity of abdominal pain/discomfort, abnormal number of bowel movements, loose or watery stools, defecatory urgency, hard or lumpy stools, straining during bowel movements, and feeling of incomplete evacuation); (2). use of resources, HRQoL, and psychological well being. METHODS: Observational, prospective, multicenter study. Symptoms were registered in a diary over two 28-day periods with an interval of 4 wk; direct resource use and indirect costs were noted weekly. Three HRQoL questionnaires were administered. RESULTS: High-intensity symptoms were present on more than 50% of the days. Sixty-one percent were classified in the same IBS subtype on both occasions (kappa= 0.48), while 49% had the same symptom predominance and intensity (kappa= 0.40). The greatest instability was observed among diarrhea (D-IBS) and constipation (C-IBS) subtypes: only 46% and 51% remained in the same pattern with a tendency to shift to alternating diarrhea/constipation subtype (A-IBS); however, practically no patient changed from D-IBS to C-IBS, or vice versa. The most reliable symptom characteristic was frequency, followed by intensity and number of episodes. Symptom frequency and intensity were directly related to resource use and HRQoL impairment. CONCLUSIONS: IBS symptoms are instable over time and variables in intensity. Many patients with D-IBS or C-IBS move to A-IBS; however, shift from D-IBS to C-IBS, or vice versa, is very infrequent.     

Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by sildenafil: effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome

OBJECTIVES: Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro. Sildenafil stimulates the nitric oxide guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS). METHODS: In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration of sildenafil (50 mg p.o.). Perception was scored on a graded scale of 0-6. At the end of a distension series an anatomic questionnaire was filled out by the subjects. RESULTS: Sildenafil significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/- 25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased by sildenafil both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged. CONCLUSIONS: Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated.     

Perceptual responses in patients with inflammatory and functional bowel disease

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.