Patients with irritable bowel syndrome (IBS) frequently report

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5: Lipid-Induced Colonic Hypersensitivity in the Irritable Bowel Syndrome: The Role of Bowel Habit, Sex, and Psychologic Factors MAGNUS SIMRÉN, HASSE ABRAHAMSSON, and EINAR S. BJÖRNSSON Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden Background & Aims: Duodenal lipid infusion increases colonic hypersensitivity in irritable bowel syndrome (IBS). Whether this is affected by bowel habit, psychologic factors, or sex is unknown. Methods: We included 61 patients with IBS (50 women, 11 men), 25 with diarrheapredominant IBS, 17 with constipation-predominant IBS, 19 with alternating-type IBS, and 20 healthy controls (15 women, 5 men). A colonic distension trial was performed with a barostat before and after a 1-hour duodenal lipid infusion (3 kcal/min). Colonic thresholds, colonic tone, and the viscerosomatic referral pattern were assessed and compared between groups. Patients also completed the Hospital Anxiety and Depression scale. Results: The reduction in colonic pressure thresholds after vs before duodenal lipids was greater in patients than in controls for discomfort (P.006) and pain (P <.0001). An increased viscerosomatic referral area for pain and discomfort during colonic distensions after vs before duodenal lipids was observed in patients but not in controls. The response was similar in IBS subgroups based on the predominant bowel habit, in patients with vs without anxiety and/or depression, and in women and men with IBS. The colonic tone response during lipid infusion was similar in IBS patients and controls, and in the different IBS subgroups. Conclusions: IBS patients show increased colonic sensitivity and altered viscerosomatic referral pattern after duodenal lipids. This response is largely unaffected by the predominant bowel habit, psychologic factors, or sex, but seems to be related to IBS per se. Patients with irritable bowel syndrome (IBS) frequently report postprandial worsening of symptoms and adverse reactions to one or more foods. 1,2 The mechanisms involved are incompletely known, but probably are related to several different factors such as exaggerated motor responses after meal intake, 3,4 abnormal colonic fermentation, 5 problems with gashandling in the gastrointestinal tract, 6 various food intolerances, 7 9 and psychologic factors. 2 Recent studies have suggested that visceral hypersensitivity is one of the most important factors behind the symptoms in IBS and other functional gastrointestinal (GI) disorders. 10 We and others recently showed that the colorectal hypersensitivity in IBS patients is exaggerated by nutrient delivery directly into the duodenum, supporting a role of visceral hypersensitivity in the postprandial symptoms in IBS patients as well. Eating a meal stimulates colonic myoelectrical and motor activity. 15,16 This gastrocolonic response consists of a gastric phase mediated by mechanoreceptors and an intestinal phase, mainly owing to the stimulation of chemoreceptors, in which the fat component of the food is the main stimulus. 17,18 There also appears to be a sensory component of the gastrocolonic response, shown by increased rectal sensitivity in healthy volunteers after a meal. 19 Fat is also the main stimulus for this sensory component of the gastrocolonic response, 20 and when lipids are delivered directly into the duodenum this response is exaggerated in patients with IBS More specifically, in our previous study 13 we showed that IBS patients had enhanced sensitivity for colonic balloon distensions after duodenal lipids as compared with control subjects, and a more pronounced increase of the area of the viscerosomatic referral during the colonic distensions after lipid administration. In a recent survey we found that female sex and anxiety predicted a high degree of subjective food intolerance in IBS patients, 2 and another study confirmed that food sensitivity is more prominent in females. 21 Moreover, the symptom pattern in IBS females differs from that in IBS males There also is some evidence in the literature that sex and psychologic factors might influence the colorectal sensitivity in this group of patients, 24,25 and a recent study also suggested gender differences in the autonomic responsiveness to a visceral stressor (ie, to balloon distension). 26 The effect of the predominant bowel habit of the IBS patient on sensitivity to food ingestion is not evident, 2 but from a physiologic point of view different responses in the IBS subgroups seem logical. 27 The evidence for a difference in colorectal sensitivity between the different IBS subgroups based on the predominant bowel habit is weak, with some studies supporting enhanced sensitivity in patients with diarrheapredominant IBS (IBS-D), 28,29 and others showing enhanced rectal sensitivity in constipation-predominant IBS (IBS-C). 30 Whether there are differences related to sex, psychologic comorbidity, or the predominant bowel habit in the colorectal sensory response to nutrients in the upper GI tract in IBS patients is largely unknown. In our previous study 13 we saw trends toward an enhanced response in IBS-D vs IBS-C, but later Caldarella et al 11 found no clear difference between these subgroups, even though the symptom specificity in response to rectal distension differed and was maintained after nutrients. However, both of these studies were limited by a relatively low number of IBS Abbreviations used in this paper: GI, gastrointestinal; HAD, Hospital Anxiety and Depression scale; 5-HT 3, 5-hydroxytryptamine 3; IBS, irritable bowel syndrome; IBS-A, IBS alternating type; IBS-C, constipationpredominant irritable bowel syndrome; IBS-D, diarrhea-predominant irritable bowel syndrome; IOP, intraoperative pressure; PVE, phasic volume event by the AGA Institute /07/$32.00 doi: /j.cgh

2 202 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 2 subjects included (n 16 in both studies), making chance findings and type II errors possible. Therefore, the aim of the present study was to evaluate the role of sex, psychologic factors, and the predominant bowel habit in the exaggerated sensory component of the gastrocolonic response in a large group of IBS patients, which might translate into differences in food sensitivity between different subgroups of IBS patients. Methods Subjects We included 61 IBS patients according to the Rome II criteria 31 (50 women; mean age, 41 y; range, y). All patients suffered from worsening of their symptoms after meal intake, and 44 of the 61 patients reported that this occurred often or always, whereas the rest experienced postprandial worsening only occasionally. Organic GI disorder was excluded with reasonable certainty, using appropriate blood tests and investigations based on the symptom patterns of the patients. Of the IBS patients, 25 had IBS-D (21 women; mean age, 42 y; range, y) and 17 had IBS-C (15 women; mean age, 40 y; range, y) according to the Rome II criteria. 31 The other 19 IBS patients had alternating diarrhea and constipation and were considered to have IBS of alternating type (IBS-A) (14 women; mean age, 42 y; range, y). All patients completed the Hospital Anxiety and Depression (HAD) scale. 32 We also included 20 healthy volunteers (15 women; mean age, 31 y; range, y). The healthy volunteers (15 women, 5 men) were significantly younger than the IBS patients (P.001), but the gender distribution in the groups was similar. All control subjects were free of GI symptoms as assessed by a GI symptom questionnaire to ensure the exclusion of nonpatients with IBS. None of the subjects was taking any medication known to affect the GI tract. All subjects gave informed consent and the study was approved by the ethics committee of the University of Göteborg. Barostat Procedure After an overnight fast the subjects took a tap-water enema (1500 ml) at home and then arrived at the hospital at 7:30 AM. Under fluoroscopic guidance an enteral feeding tube (Meda Polyuretansond; Fresenius AG, Bad Homburg, Germany) was placed with its tip in the descending part of the duodenum. The tube then was secured with tape to the cheek. Thereafter, the balloon catheter, consisting of a highly compliant polyethylene balloon attached to a double-lumen polyvinyl tube (Salem Sump Tube, 18F; Sherwood Medical, Tullamore, Ireland), was placed in the midsigmoid colon. The balloon was tied at both the proximal and distal ends and the distance between the attachment sites was 10 cm. Distension to a maximal volume of 550 ml resulted in a cylindric balloon. A thin thread was inserted through the biopsy channel of a flexible fiberoptic sigmoidoscope and tied to the tip of the balloon catheter. With the subject in the left lateral position, the balloon catheter was attached to the sigmoidoscope and passed to a level of cm from the anal verge. Retained formed stools were not observed in any of the subjects rectums or sigmoid colons during this procedure. The balloon catheter was left in place as the sigmoidoscope was removed. After this procedure the balloon catheter was connected to a computer-driven electronic barostat (Dual Drive Barostat, Distender Series II; G&J Electronics Inc., Toronto, Canada). A small number of distensions, up to 25 mm Hg, were made to unfold the balloon properly. The intraoperative pressure (IOP) then was set to 2 mm Hg above the minimal distending pressure necessary to record respiratory variations in the balloon volume. An initial conditioning distension sequence was performed, inflating the balloon by 5 mm Hg step-wise increments every 30 seconds until the subjects reported discomfort. This was performed because a previous study 33 showed that measurement of compliance and sensation are different between the first and second distension sequences, but not between the second and subsequent distension sequences. Thereafter, a 30-minute equilibrium period was allowed with the balloon pressure at IOP during which colonic tone was assessed. In addition to the conditioning distension sequence mentioned earlier, 2 distension sequences were performed: 1 before and 1 immediately after the administration of lipid solution (Calogen; Nutricia Nordica, Stockholm, Sweden, 1.5 kcal/ml) via the enteral feeding tube. The infusion rate was 2 ml/min over 1 hour. When the subjects received the infusions the balloon pressure was set at IOP. The subjects were told to report if they perceived any symptoms during the infusions. The Distensions We used phasic distensions of 30 seconds duration starting at IOP and increasing step-wise by 3 mm Hg until the subject reported pain or when a pressure of 50 mm Hg was reached. Pressure steps were used according to international recommendations. 34 The distensions were separated by resting periods of 30 seconds, with the balloon pressure set to the IOP. The subjects were instructed to grade their sensations during the distensions by using a keypad linked to the main barostat. A grading scale consisting of 7 parameters was used: 1 no sensation, 2 fullness, 3 gas, 4 discomfort, 5 pain, 6 severe pain, and 7 intolerable pain. A tracking technique (single random staircase) was used, with tracking beginning when pain (score of 5, 6, or 7) was first reported, after which 10 more distensions were performed, provided the subject reported pain for at least 3 of them. The subjects also were instructed to mark the location of their respective sensation on a body map to evaluate the viscerosomatic referral pattern. This was performed separately for each distension sequence. Barostat Data Collection The Protocol Plus software package (G&J Electronics Inc.) was used for barostat data collection. The thresholds for first sensation, gas, discomfort, and pain were determined during each distension sequence. The pain threshold was the average pressure of the distensions when pain was reported. If pain was not experienced, the pain threshold was set to the maximum pressure of 50 mm Hg. We also assessed the change in the thresholds after vs before the lipid infusion. Colonic balloon volumes, reflecting tone, were assessed with the pressure at IOP. Barostat balloon volumes were averaged over periods of 10 minutes for the 30-minute period before the distensions (fasting tone) and for the 60-minute period during the infusions, respectively. Mean volumes were thereafter calculated for the 30-minute period before the distensions representing fasting tone and for the two 30-minute periods during lipid infusion. Furthermore, the number of phasic volume events (PVEs), defined as changes of 10% or more comparative with the baseline volume, and occurring at a rate of 1 4/min, 35 were calculated during the lipid infusion. Compliance curves (ie, pressure-

3 February 2007 LIPID INDUCED COLONIC HYPERSENSITIVITY IN IBS 203 Table 1. Sensory Thresholds in Control Subjects Before Versus After Duodenal Lipid Infusion Baseline After lipids P value First sensation Pressure, mm Hg Volume, ml Gas Pressure, mm Hg Volume, ml Discomfort Pressure, mm Hg Volume, ml Pain Pressure, mm Hg Volume, ml NOTE. Sensory thresholds (mean SD) before vs after duodenal lipid infusion in the control subjects (n 20). The P values refer to withingroup comparisons between the thresholds at baseline vs after the lipid infusion. Table 2. Sensory Thresholds in IBS Patients Before Versus After Duodenal Lipid Infusion Baseline After lipids P value First sensation Pressure, mm Hg Volume, ml Gas Pressure, mm Hg Volume, ml Discomfort Pressure, mm Hg Volume, ml Pain Pressure, mm Hg Volume, ml NOTE. Sensory thresholds (mean SD) before vs after duodenal lipid infusion in IBS patients (n 61). The P values refer to within-group comparisons between the thresholds at baseline vs after the lipid infusion. volume relationships) also were created for each distension sequence and for group comparisons we used the slope of the pressure-volume curve (ie, the dynamic compliance [ml/mm Hg]). 36 To evaluate the viscerosomatic referral pattern the relative area of referred discomfort and pain was recorded by the subjects on a body map. By using a simple geometric formula this information was measured (ie, r 2 if a circle was drawn by the patient). Statistical Analysis The results are presented as mean SD unless otherwise stated. A paired t test was used to evaluate the effect of the lipid infusion on the variables assessed during the colonic distensions (ie, pressure and volume thresholds and compliance) in the IBS patients and control subjects, respectively. For comparisons between the IBS subjects and the controls, as well as between men and women with IBS, we used unpaired t tests. The results in the IBS subgroups were compared with a 1-way analysis of variance followed by post hoc analyses using a Bonferroni correction in case of a P value of less than.05. The influence of psychologic factors on the barostat results was evaluated by determining the correlation between the HAD scores and the change in colonic thresholds (Pearson correlation), and by comparing the results from the barostat experiment between patients with and without anxiety and depression using cut-off values (ie, HAD anxiety or depression score 10). 32 Generally significance was accepted at the 5% level. Results Irritable Bowel Syndrome Patients Versus Controls The lipid infusion generally was well tolerated and all subjects completed the experiments. However, during the lipid infusion 9 controls and 25 IBS subjects developed mild nausea (P NS), 8 controls and 44 IBS patients experienced mild abdominal distension (P NS), and urgency but no defecation was felt by 6 controls and 25 IBS patients (P NS); none experienced pain. The pressure thresholds in the healthy control group tended to be lower after lipid infusion compared with baseline, and this reduction was significant for discomfort (P.04) (Table 1). The corresponding volumes at the thresholds were not altered after lipid infusion compared with baseline (Table 1). In the IBS group the pressure thresholds were clearly reduced for all the sensations (Table 2). The same was true for the corresponding volumes, except for the discomfort threshold, for which only a tendency in the same direction was observed (P.08) (Table 2). All pressure and volume thresholds were significantly lower in the IBS patients than in the controls, both before and after the lipid infusion (P.05 for all comparisons). The change in threshold was significantly more pronounced in the IBS patients compared with the controls for discomfort ( vs mm Hg; P.006) and pain ( vs mm Hg; P.001), but not for first sensation ( vs ; P.3) or gas ( vs mm Hg; P.3) (Figure 1). This translates into a clearly higher proportion of patients reporting pain at a given distending pressure in patients (Figure 2A), and to a lesser degree also in control subjects (Figure 2B). The relative area of viscerosomatic referral was larger after lipid infusion compared with baseline in patients, both for discomfort ( vs cm 2 ; P.001) and pain ( vs cm 2 ; P.002), but Figure 1. The change in pressure thresholds (mm Hg; mean SD) for the different sensations during the colonic distension sequence after vs before the 1-hour lipid infusion in IBS patients (n 61) ( ) and control subjects (n 20) ( ). A negative value means a lower threshold after than before the lipid infusion. The reduction in threshold was significantly more pronounced in the IBS patients compared with the controls for discomfort and pain, but not for first sensation or gas. **P.01 vs controls.

4 204 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 2 Figure 2. The proportion of (A) patients and (B) control subjects reporting pain at a given colonic balloon pressure before ( ) and after ( 1-hour lipid infusion. ) the this pattern was not seen in healthy volunteers (discomfort: vs cm 2 ; P.9; pain: vs cm 2 ; P.5). The viscerosomatic referral area was not significantly different between controls and IBS patients at baseline, but after lipid infusion the area was larger in patients than in controls, both for discomfort (P.001) and pain (P.01). The minimal distending pressure did not differ between patients and controls ( vs mm Hg; P.7). The colonic balloon volumes were reduced significantly in both groups during duodenal lipid infusion, indirectly indicating increased colonic tone, but this response did not differ between patients and controls, neither during the first (percentage reduction of balloon volumes: 9.8% 17% vs 7.7% 25%; P.7), nor during the second 30 minute period during the lipid infusion (19% 28% vs 28% 40%; P.4). The patients had more PVEs than the controls during the lipid infusion (27 19 vs 16 15; P.02). The dynamic compliance tended to be higher during the distension sequence after vs before lipids in patients ( vs ml/mm Hg; P.19) and in control subjects ( vs ; P.03), but this did not differ between patients and controls. Irritable Bowel Syndrome Subgroups The pressure and volume thresholds did not differ between the IBS subgroups, and the change in pressure thresholds after lipid infusion compared with baseline also was similar in the IBS subgroups (Table 3, Figure 3). The viscerosomatic referral area tended to be larger in the IBS-C group vs the other IBS subgroups after lipid infusion, but this failed to reach statistical significance, both for discomfort (P.13) and pain (P.07). The percentage change in colonic balloon volumes during lipid infusion indirectly reflecting the colonic tone re- Table 3. IBS Subgroups IBS-A (n 19) IBS-C (n 17) IBS-D (n 25) P value Thresholds at baseline, mm Hg First sensation Gas Discomfort Pain Thresholds after lipids, mm Hg First sensation Gas Discomfort Pain Viscerosomatic referral area, cm 2 Discomfort, baseline Discomfort, after lipids Pain, baseline Pain, after lipids Colonic balloon volumes during lipids Reduction 0 30 min, % Reduction min, % PVEs Dynamic compliance, ml/mm Hg Baseline After lipids

5 February 2007 LIPID INDUCED COLONIC HYPERSENSITIVITY IN IBS 205 Table 4. Correlation Coefficients Obtained Using Pearson Correlation Between Scores for Anxiety and Depression on the HAD Scale and Changes in Pressure Thresholds After Versus Before the Lipid Infusion First sensation Gas Discomfort Pain Figure 3. The change in pressure thresholds (mm Hg; mean SD) for the different sensations during the colonic distension sequence after vs before the 1-hour lipid infusion in the IBS subgroups based on the predominant bowel habit., IBS-A (n 19);, IBS-C (n 17);, IBS-D (n 25). A negative value means a lower threshold after lipids than at baseline before the lipid infusion. No significant group differences were seen. sponse also was similar in the subgroups, and this also was true for the number of PVEs. The colonic compliance was similar in the subgroups both before and after the lipid infusion. Patients who reported food-related symptoms often or always had a greater reduction of the pain threshold after lipid infusion vs before than those with postprandial symptoms occurring only occasionally (24% 22% vs 9.8% 20%; P.04). Otherwise no differences between these groups were found. Sex The pressure and volume thresholds did not differ between women and men with IBS (data not shown), and the change in threshold after lipid infusion compared with baseline also was similar in female and male IBS patients, except for a greater reduction of the pressure threshold for first sensation in women (P.02) (Figure 4). The viscerosomatic referral area for pain was larger in women than in men, and this difference reached statistical significance at baseline ( vs cm 2 ; P.006), but only a tendency in the same direction was seen after lipids (15 16 vs cm 2 ; P.10). The percentage change in colonic balloon volumes during lipid infusion also was similar in men and women, and this also was true for the number of PVEs and the dynamic compliance (data not shown). HAD-Anxiety HAD-Depression Anxiety and Depression Based on cut-off levels on the HAD scale, 17 IBS patients had clinically significant anxiety and 13 patients had depression. There were no significant correlations between the scores on the HAD and the change in pressure thresholds after lipid infusion compared with baseline (Table 4). The pressure and volume thresholds did not differ between IBS patients with and without anxiety or depression (data not shown), and the change in threshold after lipid infusion compared with baseline also was similar (Figure 5). There were also no differences when comparing patients with anxiety and/or depression with patients with neither anxiety nor depression (data not shown). No differences were seen in colonic compliance, percentage change in colonic balloon volumes, or the number of PVEs between patients with vs without anxiety and/or depression, and the viscerosomatic referral pattern also was unrelated to the HAD scores (data not shown). Discussion In the present study we have confirmed previous results from smaller studies, showing enhancement of colorectal sensitivity after the delivery of lipids into the duodenum in this group of patients The present study increases the previous knowledge by showing that this response in IBS seems to be largely unaffected by the predominant bowel habit of the pa- Figure 4. The change in pressure thresholds (mm Hg; mean SD) for the different sensations during the colonic distension sequence after vs before the 1-hour lipid infusion in women (n 50) and men (n 11) with IBS. A negative value means a lower threshold after than before the lipid infusion. No significant group differences were seen. *P.05., Women;, men. Figure 5. The change in pressure thresholds (mm Hg; mean SD) for the different sensations during the colonic distension sequence after vs before the 1-hour lipid infusion in IBS patients with vs without clinically significant anxiety or depression based on cut-off levels on the HAD scale. A negative value means a lower threshold after lipids than at baseline before the lipid infusion. No significant group differences were seen., Anxiety (n 17);, no anxiety (n 44);, depression (n 13);, no depression (n 48).

6 206 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 2 tient, the patient s sex, and the presence or absence of anxiety and depression. This enhancement of colonic sensitivity after duodenal lipids may be an important factor in the development of postprandial symptoms in IBS. In our previous study in 16 patients with IBS, we found that their colonic sensory thresholds decreased after duodenal lipids and they also showed an altered viscerosomatic referral pattern, which was not seen after saline infusion into the duodenum (control). 13 The control subjects in that study also had reduced sensory thresholds after duodenal lipids, although the reduction was not as pronounced as in the patients and the viscerosomatic referral pattern remained unaltered. These findings led us to the conclusion that IBS patients show an exaggerated sensory component of the gastrocolonic response. Our current study with a larger IBS sample has confirmed these findings, and after our initial study there also have been other studies assessing the effects of nutrient delivery directly into the duodenum on colorectal sensitivity in IBS and have confirmed this exaggerated response. 11,12,14 We believe that these findings, together with postprandial motor alterations in IBS, 3,4,37 abnormal colonic fermentation, 5 problems with gas-handling in the GI tract, 6 various food intolerances, 7 9 and psychologic factors 2 may explain meal-related symptoms in IBS patients. The mechanism behind the enhancement of colonic sensitivity after nutrient delivery into the upper GI tract in IBS patients remains uncertain. The motor component of the gastrocolonic response is mediated via cholinergic neurons and possibly also opiate receptors, whereas cholecystokinin, although proposed to be a physiologic mediator of intestinal motility in human beings, 41 is probably not important in the colonic response to feeding. 42 Recent studies have revealed that 5-hydroxytryptamine 3 (5-HT 3 ) receptors participate in the human gastrocolonic motor response 35 and 5-HT 3 receptor antagonism blunts both the mechanoreceptor and chemoreceptor components of this response. 43 However, in a recent study, alosetron, a 5-HT 3 receptor antagonist, only partially diminished the exaggerated sensory component in IBS patients as compared with placebo, and therefore 5-HT 3 receptors seem not to be the principal mediator, but may be a cofactor for the exaggerated sensory component of the gastrocolonic response in IBS. 44 Also, hypnotherapy reduced this response in IBS patients to some extent as compared with supportive therapy, indirectly proposing that central factors also might be involved in this response. 45 Another possibility is that the exaggerated sensory response is a reflection of an abnormal sensitivity to the physiologic cholecystokinin release in response to lipids. 46 It has been shown that cholecystokinin octapeptide can provoke abnormal reactions of the gall bladder in IBS patients, 47 higher pain scores in patients with functional abdominal pain, 48 and unmask gut dysmotility in IBS. 49 Moreover, after lipid delivery into the upper gut a wide array of other hormones/neuropeptides are released, and several of these also might be involved in this enhancement of colonic sensitivity in IBS patients after duodenal lipids. The motor response to the meal, which has been shown to be exaggerated in IBS in terms of myoelectrical and phasic motor activity, 3,37,50 also may be involved in the enhanced colonic sensory response after duodenal lipids in IBS. We only evaluated the tone response and the dynamic compliance, which did not differ between the groups, and phasic volume events, which were more frequent in patients. This was also the case during saline infusion in our previous study, 13 making it unlikely that this could explain the different sensory responses between patients and controls. However, the motor response in other parts of the colon was not evaluated using, for instance, simultaneous manometry. It has been shown that repetitive sigmoid distensions increase rectal sensitivity in IBS patients but not in controls, probably through central sensitization at the dorsal horn level. 51 With these results in mind, it is possible that an exaggerated motor response in the colon, not specifically at the site of the balloon, may have produced increased sensitivity in the sigmoid colon in the IBS patients, but not in the controls, as part of the defective viscerosensory processing in these patients. 52 The administration of lipids in the duodenum separated the IBS patients from the controls more clearly when assessing the sensory thresholds and viscerosomatic referral pattern. However, this model did not differentiate the IBS patients from healthy subjects completely because a small number of controls also were quite sensitive to colonic distensions, without suffering from GI symptoms. It is conceivable that several different stimuli with known effects on visceral perception, such as nutrients, psychologic stress, 53 colonic stimulation with balloon distensions, 51 and sympathetic activation, 54 should be applied simultaneously to differentiate patients from controls in a better way. More work needs to be performed to come up with a diagnostic tool that separates IBS patients adequately from healthy subjects. We found only minor effects on the response in women and men with IBS, most likely of no major clinical importance. The majority of variables did not differ between men and women, which are in line with a recent study reporting no clear difference in visceral sensitivity between men and women with IBS. 55 However, one should bear in mind that the number of men included in our study was rather small (n 11). Also, psychologic factors have been proposed to be of importance for visceral sensitivity in IBS. 56 However, in this study we could not find evidence to support this because the severity of anxiety and depression, assessed by the widely used HAD scale, 32 did not influence our findings at all. The third possibly confounding factor assessed in this study was the IBS subgroup based on the predominant bowel habit of the patient. Obviously these patients have different symptoms related to their bowel habit and there also is some evidence to support differences in other symptoms, such as bloating and extraintestinal symptoms. 57 The effect of the predominant bowel habit on visceral sensitivity differs between studies. 28,30,58 In this study we could not find any differences between the IBS subgroups, neither in motor nor in sensory parameters. These findings implicate that the exaggerated sensory component of the gastrocolonic response is related to IBS per se, and not to a specific subgroup of IBS patients based on bowel habit, sex, or psychologic comorbidity. To conclude, IBS patients show increased colonic sensitivity and altered viscerosomatic referral pattern after duodenal lipids. This response is largely unaffected by the predominant bowel habit, psychologic factors, or sex, but seems to be related to IBS as such. This enhancement of colonic sensitivity after administration of lipids in the upper GI tract may be one important factor in the development of postprandial symptoms in IBS.

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