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Keywords:

  • barostat;
  • compliance;
  • irritable bowel syndrome;
  • recto-colonic reflex;
  • visceroperception

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Abstract  Motor and sensory dysfunction of the gut are present in a subset of patients with irritable bowel syndrome (IBS). Recent studies have demonstrated the presence of a recto-colonic inhibitory reflex in healthy humans. It is not known whether this reflex exists in IBS. We studied rectal compliance, perception and the recto-colonic reflex by measuring volume responses of the descending colon to rectal distentions by barostat in 26 IBS patients and 13 healthy controls under both fasting and postprandial conditions. In the fasting state, rectal distention inhibited colonic tone and phasic motility to a similar extent in health and IBS. After a meal, rectal distention inhibited colonic tone and phasic motility to a lesser degree (P < 0.05) in IBS than health. Under postprandial but not fasting conditions, rectal distentions of increasing intensity were associated with higher pain scores in IBS than in health. Rectal distention inhibits tonic and phasic motility of the descending colon in healthy controls and in IBS patients. Postprandially this recto-colonic inhibitory reflex is impaired and attenuated in IBS patients compared with controls. These findings point to an altered reflex function in IBS and have implications for pathophysiology and therapy.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Irritable bowel syndrome (IBS) is a functional bowel disorder that affects 5–20% of the general population and is characterized by recurrent abdominal pain and disturbed bowel habits.1,2 The pathophysiology of IBS is poorly understood, but disturbances at various levels of the brain–gut axis have been identified, including postinflammatory changes,3 inappropriate mucosal immune activation,4,5 hyperexcitability of spinal dorsal horn neurones6 and altered central processing of sensory afferent information.7 These alterations may result in visceral hypersensitivity, which is considered a hallmark of IBS.8 In addition, motor dysfunction may occur in IBS. However, disturbed gut motor and sensory functions are present only in a subset of IBS patients, emphasizing the need for alternative explanations for the pathophysiology of IBS.

Reflex inhibition of proximal gastrointestinal motor activity in response to stimulation of a distal segment of the small bowel has been demonstrated in healthy individuals.9,10 Recent observations in humans11–13 suggest the presence of recto-colonic and colorectal reflexes in the large bowel. These reflexes differ from the peristaltic reflex as they affect intestinal motility at much more distant segments. To date, the recto-colonic reflex has not been characterized in IBS.

Symptoms in IBS are typically provoked by a meal or, when already present, deteriorate postprandially. Simren et al. demonstrated that duodenal lipid perfusion reduces perception thresholds for first sensation, gas, discomfort and pain in IBS patients, but only for gas in healthy controls.14 These data suggest an exaggerated sensory response to a meal in IBS. Our aim was to evaluate the recto-colonic reflex in IBS patients under both fasting and postprandial conditions and to compare the results with those obtained in healthy controls.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Subjects

Twenty-six IBS patients between 18 and 65 years of age were recruited at the outpatient department of Gastroenterology and Hepatology of the Leiden University Medical Centre (LUMC). The diagnosis of IBS was based on Rome II criteria.2 Medication for IBS was permitted but had to be stopped 4 days prior to the experiment. Thirteen healthy control subjects were recruited through advertisement. All participants provided informed consent and the LUMC ethics committee had approved the study protocol. Patient characteristics are shown in Table 1.

Table 1.   Baseline characteristics of irritable bowel syndrome (IBS) patients and controls
 IBS (n = 26)Controls (n = 13)
Age (years)40.5 ± 15.837.2 ± 11.3
Females, N (%)16 (62)6 (46)
Bowel habit, N (%)
 Diarrhoea11 (42)0
 Constipation5 (19)0
 Alternating10 (39)0
 Normal013 (100)

Barostat

Two electronic barostats (Synectics Visceral Stimulator, Synectics Medical, Stockholm, Sweden) were used to study the recto-colonic reflex. One barostat was used to perform phasic rectal distentions, while the other measured changes in colonic tone. Pressure and volume were continuously monitored and recorded on a personal computer (Polygram for Windows SVS module; Synectics Medical). The barostat assembly is illustrated in Fig. 1.

image

Figure 1.  Dual barostat assembly with one bag in the rectum (R) and one bag in the descending colon (C). Both bags are connected to separate barostats.

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Experimental design

All experiments were performed on one day to reduce subject discomfort. Therefore, we were unable to randomize the intervention (meal vs fasting), but all measurements were performed in the same order, i.e. first under fasting and thereafter under fed conditions.

The bowel was cleansed with 2 L of polyethylene glycol (KleanPrep®, Norgine B.V., Amsterdam, the Netherlands) the day before the experiment. After an overnight fast, subjects reported at our department at 7.30 am and received a tap water enema. A flexible guide wire was placed in the transverse colon by endoscopy. A barostat catheter with bag was then positioned over the guide wire into the descending colon under fluoroscopic control. A second barostat catheter was placed in the rectum, approximately 5 cm from the anal verge. Experiments were performed with subjects in a 10° recumbent supine position (Trendelenburg), lying in a bed.

The experimental protocol is illustrated in Fig. 2. After a 30-min resting period, colonic operating pressure (OP; defined as the pressure that provides a continuous intrabag volume of 80 mL) was determined during slow ramp distention (1 mmHg min−1 increments until 80 mL bag volume was reached). Colonic bag pressure was then set at OP and kept constant throughout the experiment. After 30 min, a rectal distention protocol was started, consisting of five phasic bag distentions of 10, 15, 20, 25 and 30 mmHg of 5 min duration each. Each distention was followed by a 5-min rest period at 5 mmHg. The rectal distention protocol ended after 50 min and was followed by a 30-min rest period while maintaining colonic bag pressure. After 15 min, subjects ingested a 200 mL liquid test meal (NutrisonTM, Nutricia, Zoetermeer, The Netherlands; 600 kCal; 13% proteins, 48% carbohydrates, 39% fat). The rectal distention protocol was repeated 15 min after the onset of meal ingestion. An additional 40 mL of NutrisonTM was administered at the beginning of each rectal distention to maintain a nutritional steady-state during the experiment. At the end of the experiment, the position of both bags was checked using fluoroscopy, and the bags were removed.

image

Figure 2.  Experimental design. Two identical phasic rectal distention paradigms were performed during fasting and after meal ingestion, while colonic bag pressure was set at operating pressure. Meal ingestion consisted of 200 mL of NutridrinkTM (t = 115 min, black circle), followed by 40 mL of NutridrinkTM at the beginning of each rectal distention (grey circles). Urge and pain perception was scored at 30 s after rectal distention onset (triangles).

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The perception of urge to defecate and abdominal pain was quantified on a 100-mm visual analogue scale (VAS) at 30 s after the onset of each rectal distention, with end points ranging from ‘none’ to ‘unbearable’.

Data analysis

Rectal compliance was calculated by measuring the slope of the volume–pressure relationship from the onset of distention until the maximum pressure was reached. Mean colonic volumes during rectal distention were computed per minute. Subsequently, the relative change was calculated as the maximal colonic volume per distention divided by the average colonic volume in the 5-min predistention period (baseline volume). Phasic motility was defined as a 10% volume reduction below baseline, lasting for 10–60 s, and expressed as number of phasic volume events (PVEs) per 5 min.

Statistical analysis

Linear mixed model analysis (spss for Windows 11.0.1, SPSS Inc., Chicago, IL, USA) was performed to detect differences in colonic bag volume changes, perception scores and number of PVEs, over time, between patients and controls. Group, condition (rectal distention level) and group by condition interaction were analysed as separate contributors to the model. Between-group differences were compared by unpaired t-statistics or Mann–Whitney tests. Data are expressed as mean ± SD. P-values of <0.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Baseline barostat characteristics

Rectal compliance was reduced in IBS patients compared with controls, but the difference was only significant in the fed state (patients vs controls, fasting state: 101 ± 35 mL per 5 mmHg vs 131 ± 86 mL per 5 mmHg, P = 0.13; Fig. 3A; fed state 110 ± 37 mL per 5 mmHg vs 140 ± 52 mL per 5 mmHg, P = 0.05; Fig. 3B). However, analysis of covariance showed that postprandial compliance was not significantly different between health and IBS after adjusting for fasting compliance. No significant differences between patients and controls were found in baseline OP, colonic bag volumes and number of PVEs in the fasting state and colonic volumes and number of PVEs in the postprandial state (Table 2).

image

Figure 3.  Rectal compliance expressed as mean volumes (mL ± SEM) during successive distentions in healthy control subjects (triangles/squares) and irritable bowel syndrome patients under fasting (A) and postprandial conditions (B).

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Table 2.   Baseline barostat characteristics of IBS patients and controls
 IBS patientsControlsP-value
  1. PVE, phasic volume event; IBS, irritable bowel syndrome.

Fasting
 Operating pressure (mmHg)14.5 ± 4.512.6 ± 4.00.21
 Baseline colonic volume (mL)137 ± 42122 ± 330.26
 PVEs (N per 5 min in predistention episode)2.9 ± 2.83.7 ± 2.80.42
Postprandial
 Baseline colonic volume (mL)145 ± 42125 ± 550.21
 PVEs (N per 5 min in predistention episode)4.6 ± 2.34.3 ± 3.00.70

Colonic volume during rectal distentions

Relative colonic bag volumes during rectal distentions in the fasting state are illustrated in Fig. 4A. Mixed model analysis showed that colonic volumes differed across rectal distentions (condition, P < 0.001). However, the magnitude of colonic relaxation was not different between IBS patients and healthy controls (interaction, P = 0.70). Fig. 5 represents an example of the colonic tracing during fasting in a healthy control subject.

image

Figure 4.  Colonic bag volumes (% ± SEM) relative to baseline during rectal distentions in healthy control subjects (grey bars) and irritable bowel syndrome patients (black bars) under fasting (A) and postprandial conditions (B).

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image

Figure 5.  Example of a colonic volume tracing (upper curve) during increasing phasic rectal distentions (lower curve) in a healthy volunteer. From 15 mmHg onward, colonic volume increases while the number of phasic volume events is reduced. The colonic bag volume returns to baseline after the rectal distention protocol has ended.

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During the postprandial period, the interaction between condition and group was significant (P = 0.01), suggesting that the effect of rectal distention on colonic volume differed between patients and controls. Fig. 4B suggests that colonic relaxation was less pronounced in IBS than in health.

Phasic motility

During fasting, rectal distentions inhibited colonic motility, reflected by reduced number of PVEs to a similar degree in both groups (condition, P < 0.001; group by condition interaction, P = 0.41; Fig. 6A).

image

Figure 6.  Number of colonic phasic volume events (±SEM) at baseline and during rectal distentions in healthy controls (grey bars) and irritable bowel syndrome patients (black bars) under fasting (A) and postprandial conditions (B).

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In the absence of rectal distention, more PVEs were observed after compared with before a meal. The increase was significant in IBS patients from 3.4 ± 2.6 to 4.6 ± 2.3 PVEs per 5 min (P = 0.02), but not in controls (from 3.9 ± 3.4 to 4.3 ± 3.0 PVEs per 5 min, P = 0.52). During rectal distention after a meal, analysis of colonic PVEs revealed an interaction (P < 0.05) between condition and group. Fig. 6B suggests that more PVEs occurred in patients compared with controls.

Perception

Urge

During fasting, urge scores increased similarly in patients and controls at increasing bag pressures (condition, P < 0.001; group by condition interaction, P = 0.87; Fig. 7A). Similarly, urge increased significantly in both groups after the meal (condition, P < 0.001), without significant between-group differences (P = 0.95 for the interaction).

image

Figure 7.  (A) Perception of urge to defecate during fasting in patients (open squares) and controls (open triangles) and after meal ingestion in patients (closed squares) and controls (closed triangles). (B) Pain perception during fasting in patients (open squares) and controls (open triangles) and after meal ingestion in patients (closed squares) and controls (closed triangles).

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Pain

Under fasting conditions, pain scores in patients appeared higher compared with controls, but the interaction was not significant (P = 0.08; Fig. 7B). Postprandially, the group by condition interaction for pain was significant (P = 0.01). Fig. 7B shows that pain after a meal was increased in IBS patients compared with controls.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

This is the first study to compare fasting and postprandial recto-colonic reflexes in health and IBS. Colonic motility was characterized by assessing tone and PVEs with a barostat. Our results show that (i) in controls, colonic tone and PVEs decline during rectal distention under fasting and postprandial conditions, (ii) during fasting, colonic relaxation during rectal distention is comparable between IBS patients and healthy controls and (iii) after a standardized meal, colonic relaxation during rectal distention is impaired in IBS patients compared with controls. Under fasting conditions, rectal distention inhibited colonic tone and PVEs in an intensity-dependent manner in both health and IBS.

Reflex inhibition of colonic motility during rectal distention has previously been demonstrated in humans. Law et al. showed that colonic bag volumes increased during ramp and phasic rectal distentions in healthy volunteers.11 In addition, our results also suggest for the first time that the magnitude of colonic relaxation is related to the intensity of rectal distention during fasting conditions. In contrast, Ng et al. reported that while seven of 14 subjects exhibited colonic dilatation during rectal distention, there was no significant overall group response.12 Among our healthy subjects, colonic volumes increased by 10% or more in nine of 13 subjects during rectal distention by 25 mmHg and in 10 of 13 subjects during 30 mmHg distention. Our results therefore support the observations by Law et al.11 that a recto-colonic inhibitory reflex exists in humans. Differences in study design may explain the discrepancy between our study and this previous study.12 For instance, Ng et al. studied the colonic volume response to only one rectal distention, while in our study and that of Law et al. several rectal distentions were employed and a dose–response relationship could be established. Recently, Ng et al. studied the colorectal reflex by dual barostat assembly and found the reflex to be significantly attenuated in IBS patients compared with controls.13

Under postprandial conditions, reflex inhibition of colonic motility, as measured by colonic volumes, was impaired in IBS patients compared with healthy controls. It is unlikely that the differences were attributable to differences in baseline colonic bag volumes, which were not significantly different. However, similar to previous studies, IBS patients had an exaggerated postprandial colonic contractile response.15,16 Perhaps, exaggerated postprandial colonic motor activity impairs the ability of the colon to relax and thereby attenuates rectocolonic reflexes in IBS patients after a meal.

Consistent with previous studies, pain scores during rectal distentions were higher in IBS patients than in controls.8,17 Furthermore, patients experienced more pain in the fed state compared with controls, while preprandial pain scores were not different between groups. Simren et al. showed that duodenal lipid infusion reduced perception thresholds for first sensation, gas, discomfort and pain in IBS patients, but only for gas in healthy controls,14 suggesting an exaggerated sensory response to a meal or nutrients in IBS patients. Recently, Caldarella et al. demonstrated that intraduodenal infusion of lipids reduced thresholds for discomfort during rectal distention in IBS patients, but not in healthy controls. However, thresholds for perception were significantly lower in IBS compared with controls, with no additional effect of lipid infusion.18 Our findings confirm these results, and clinical observations suggest that IBS symptoms deteriorate after a meal. However, the repeated distentions in our study may also have contributed to increased postprandial pain perception.19

The role of postprandial recto-colonic inhibitory reflexes in the pathophysiology of IBS is not clear. Recent reports point to impaired reflexes at other locations in the gastrointestinal tract in patients with functional bowel disorders. For instance, impaired reflex fundic relaxation following intestinal administration of nutrients has been shown in patients with functional dyspepsia.20 Our finding that colonic relaxation during rectal distention is impaired after a meal, taken together with the more pronounced effect of a meal on rectal sensation in IBS compared with controls, is consistent with the hypothesis of a generalized disturbance of postprandial colonic sensori-motor functions in IBS. This impairment should primarily be looked upon as a marker of disturbed gastrointestinal motor and sensory function, perhaps attributable to autonomic dysfunctions. In addition, disordered reflexes may also contribute to IBS symptoms, particularly postprandial exacerbation.

Finally, all measurements were performed in the same order, i.e. increasing rectal pressure distentions during fasting conditions followed by the same sequence after a meal. This was carried out to minimize discomfort to participating subjects. This is, however, a potential limitation of the study.

In conclusion, we have demonstrated the existence of a recto-colonic inhibitory reflex in healthy individuals and in IBS patients. The magnitude of this response is in the same range in both groups under fasting conditions, but is impaired in IBS patients after a meal. As the role of disturbed colonic motor and sensory function in IBS has not been fully elucidated, future studies should focus on the involvement of retrograde reflexes in the pathophysiology of functional bowel disorders and characterize recto-colonic reflex dysfunction in IBS subgroups.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
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