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.     

Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome

Abstract  Evidence suggests that patients with irritable bowel syndrome (IBS) are hyper-responsive to environmental, physical and visceral stimuli. IBS patients also frequently report poor sleep quality. This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS ( n  = 30) and healthy controls ( n  = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhoea ( n  = 14), IBS-constipation ( n  = 7) and IBS-alternators ( n  = 9). Cortisol was measured from serial blood samples drawn every 20 min, and catecholamines every hour, in a sleep laboratory from 8  pm until awakening. Because of the varied sleep schedules of the individual participants, each subject's hormone series time base was referenced with respect to their onset of Stage 2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, women with constipation-predominant IBS demonstrated significantly increased noradrenaline, adrenaline and cortisol levels throughout the sleep interval, and women with diarrhoea-predominant IBS were significantly lower on noradrenaline and cortisol. These results suggest that differences in neuroendocrine levels during sleep among IBS predominant bowel pattern subgroups may be greater than differences between IBS women and controls. Neuroendocrine profiles during sleep may contribute to our understanding of symptom expression in IBS.     

Perceptual sensitivity and response bias during rectal distension in patients with irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) report an increased frequency of sensations during rectal distension in comparison with healthy subjects. This alteration might be due to a psychological response bias leading patients to over report their sensations. The aim of this study was to measure perceptual sensitivity and response bias during rectal distension in healthy subjects and IBS patients using the sensory decision theory (SDT). Thirteen healthy subjects and 22 IBS patients underwent five rectal distensions up to 100 mL, five up to 200 mL and five sham distensions. They were asked to identify the distension by means of an electronic marker. Perceptual sensitivity and response bias were calculated according to the SDT. The patients identified a more 100 mL distensions than the healthy subjects (P = 0.02), whereas there was no difference in the number of identified 200 mL and sham distensions between the two groups. The perceptual sensitivity of IBS patients was significantly greater during 100 mL (P = 0.01), but not during 200 mL distensions. The response bias was not significantly different between the two groups. These data suggest that the increased frequency of sensations reported by IBS patients is not due to a psychological response bias.     

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.     

Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress

Abstract  Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although the issue is still under debate. The aim of this study was to determine the prevalence of SIBO in those with IBS and its association with colonic motility, bowel symptoms and psychological distress. Sucrose hydrogen and methane breath tests were performed in 158 IBS patients and 34 healthy controls (HC). Thresholds for pain and urgency were tested by barostat in the descending colon. The motility index (MI) was calculated as the average area under the curve for all phasic contractions. Questionnaires assessed psychological distress, IBS symptom severity (IBS-SS), IBS quality of life (IBS-QOL) and self-reported bowel symptoms. Fifty-two of 158 (32.9%) IBS patients had abnormal breath tests compared with six of 34 (17.9%) HC (χ² = 0.079). SIBO (SIBO+) and non-SIBO (SIBO−) patients did not differ in the prevalence of IBS subtypes, IBS-SS, IBS-QOL and psychological distress variables. IBS patients had a greater post-distension increase in MI than HC, but there was no difference between SIBO+ and SIBO− patients. Predominant methane producers had higher urge thresholds (28.4 vs 18.3, P  < 0.05) and higher baseline MI (461 vs 301.45, P  < 0.05) than SIBO− IBS patients, and they reported more 'hard or lumpy stools' when compared with predominant hydrogen producers ( P  < 0.05) and SIBO− IBS patients ( P  < 0.05). SIBO is unlikely to contribute significantly to the pathogenesis of IBS. Methane production is associated with constipation.     

Associations between postprandial symptoms,hydrogen and methane production,and transit time in irritable bowel syndrome

Background

Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients.

Methods

We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires.

Key Results

After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT.

Conclusion and Inferences

This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.     

Distension technique influences the relationship between colonic and rectal hypersensitivity in irritable bowel syndrome

In irritable bowel syndrome (IBS), it remains unclear whether rectal hypersensitivity is a 'marker' of colonic hypersensitivity. Our aim was to examine the relation between colonic and rectal sensitivity in IBS patients, comprising phasic and ramp distension techniques. Twenty IBS patients and 12 healthy subjects (N) underwent stepwise ramp and random phasic barostat distensions in the colon and rectum in random order. The sensory threshold pressure (ramp distension) and the visual analogue scale score (VAS, phasic distension), for pain and non-pain, were recorded. Colonic thresholds were lower, and VAS scores were generally higher, for pain and non-pain sensitivities in IBS compared to N. Rectal thresholds were lower, and VAS scores were higher, for pain but not for non-pain, in IBS compared to N. In IBS, for phasic distension, there was good correlation between the colon and rectum for non-pain (e.g. at 16 mmHg, r=0.59, P=0.006) and pain (r=0.60, P=0.006) sensitivities. In contrast, there was no significant correlation between the colon and rectum for ramp distension. In conclusion, colonic and rectal sensitivity in IBS are correlated in response to phasic but not ramp barostat distensions. The rectum serves as a legitimate 'window' for evaluating colonic hypersensitivity in IBS, provided that phasic distensions are employed.     

Subjective theories of illness and clinical and psychological outcomes in patients with irritable bowel syndrome

Objectives

Patients' ideas about the nature, cause, and treatment of their illnesses are part of the complex process of coping with illness. To date, limited research on subjective theories of illness in patients with irritable bowel syndrome (IBS) has been performed. The aim of the study was to investigate patients' subjective theories of illness and how these are related to clinical and psychological outcome criteria, in particular IBS symptom severity and quality of life.

Methods

Eighty-eight patients with IBS, as defined by Rome III criteria, were administered a battery of questionnaires to collect the following data: sociodemographic variables, subjective theories of illness (Subjektive Krankheitstheorien, Cause Questionnaire), anxiety (Hospital Anxiety and Depression Scale), depression (Beck Depression Inventory), quality of life (SF-12), and IBS symptoms (Questionnaire for Gastrointestinal Symptoms).

Results

Almost all patients reported theories of illness reflecting their subjective causal assumptions. The most frequently mentioned causal factors were physical illness, intrapsychic factors, and stress.Patients with mainly somatic attributions had higher IBS symptoms scores (P<.05) and reduced physical quality of life. Intrapsychic attributions were associated with reduced mental quality of life and enhanced physical quality of life (P<.01). All correlations were independent of gender, age, and irritable bowel subgroups.

Conclusions

Subjective theories of illness can have significant implications for IBS symptom severity, as well as for physical and mental quality of life.     

Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome

The objective of this study was to determine whether or not the number of enteroendocrine cells (ECs) in the gut is related to visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS). Twenty-five subjects with D-IBS (mean, 43.1 years; 16 women, nine men) were recruited into our study, along with 13 healthy controls (mean, 40.7 years; nine women, four men). Maximally tolerable pressures were evaluated via barostat testing, and the levels of ECs were immunohistochemically identified and quantified via image analysis. The numbers of ECs between the D-IBS subjects and the controls were not significantly different in the terminal ileum, ascending colon and rectum. However, the maximally tolerable pressures determined in the D-IBS subjects were significantly lower than those of the control subjects (P < 0.01), and we detected a significant relationship between the maximally tolerable pressures and the numbers of ECs in the rectum (r = -0.37, P < 0.01). Rectal sensitivity was enhanced to a greater degree in D-IBS patients exhibiting an elevated level of rectal ECs. This study provides some evidence to suggest that ECs play an important role in visceral hypersensitivity.     

Options for patients with irritable bowel syndrome: contrasting traditional and novel serotonergic therapies

This article reviews the efficacy and tolerability of traditional therapies for irritable bowel syndrome (IBS) and concludes that they are limited by both poor efficacy and adverse effects. Serotonin, a neurotransmitter found mainly in the gut, appears to represent a link in IBS pathophysiological processes -- altered gut motility, abnormal intestinal secretion and visceral hypersensitivity. Recently, available treatments for IBS have targeted serotonin receptors that are involved in motor, sensory and secretory functions of the gut. Serotonergic agents, such as alosetron (a 5-HT3 receptor antagonist) and tegaserod (a selective 5-HT4 receptor partial agonist), provide global relief of the multiple symptoms of IBS with diarrhoea and IBS with constipation, respectively, and represent important additions to the IBS treatment armamentarium.     

Sensory signalling effects of tegaserod in patients with irritable bowel syndrome with constipation.

Tegaserod relieves overall and multiple individual constipation-predominant irritable bowel syndrome (IBS-C) symptoms. However, mechanisms for the relief of abdominal pain/discomfort are not well understood. The effects of tegaserod on rectal sensitivity to distension were measured by the nociceptive flexion RIII reflex, as evidenced by spinal hyperexcitability (i.e. increase or facilitation of the RIII reflex), in IBS-C patients. A randomized, double-blind, placebo-controlled, parallel study was performed in 30 women with IBS-C. The effects of slow ramp rectal distension on the RIII reflex, recorded from the lower limb, were measured before [first experimental day (D1)] and after 7 days [day 8 (D8)] of placebo (n=15) or 6 mg tegaserod bid (n=15). Pressure-volume and sensation-volume relationships were measured during distension, and patients reported their IBS symptoms daily. On D1, rectal distension facilitated the RIII reflex in both treatment groups. On D8 vs D1 these facilitatory effects were significantly lower (P<0.001, analysis of variance) after tegaserod (mean reduction: -30.3+/-11.9%) than placebo (mean reduction: -10.1+/-12.9%). No significant changes in the volume-sensation relationship or differences in compliance were observed with tegaserod or placebo. In conclusion, tegaserod reduces the facilitatory effects of rectal distension on the RIII reflex in women with IBS-C.