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Changes in Tolerance to Rectal Distension Correlate With Changes in Psychological State in Patients With Severe Irritable Bowel Syndrome

From the School of Psychiatry and Behavioural Science, University of Manchester, Manchester, UK (E.G., J.R., B.T., F.C.); Section of Gastrointestinal Science, Hope Hospital, Manchester, UK (J.B. D.G.T.); and University of Sheffield Centre for Human Nutrition, Northern General Hospital, Manchester, UK (L.F., N.R.).

Address correspondence and reprint requests to Professor Francis Creed School of Psychiatry and Behavioural Science, Rawnsley Building, Oxford Road, Manchester M13 9WL, UK. E-mail: francis.creed{at}man.ac.uk

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: Reduced tolerance to rectal distension has been regarded as a biological marker for irritable bowel syndrome (IBS), but longitudinal studies are few. This study determined whether change in tolerance to rectal distension after psychological treatments was associated with: 1) change in abdominal pain; 2) change in psychological symptoms; 3) a reported history of sexual abuse.

METHODS: Participants completed a visual analogue scale of abdominal pain, SCL-90 and Hamilton rating scale of depression; discomfort threshold to rectal distension was determined using a double random staircase protocol. These were measured at entry to a trial of psychotherapy or paroxetine (selective serotonin reuptake inhibitor antidepressant) and 3 months later (N = 52). Analysis of change scores were adjusted for treatment group and baseline values.

RESULTS: Increased tolerance to distension after treatment was associated with reduction in depression (r = –0.37, p = .008) but not abdominal pain. Patients who reported prior sexual abuse showed greater increase in tolerance than the remainder (changes in volume threshold: –24.7 ml [SEM = 12.1] vs. 3.6 ml [SEM = 6.2], adjusted p = .045; changes in pressure threshold: –4.7 [SEM = 1.7] mm Hg vs. 0.96 [SEM=0.9], adjusted p = .005). Multiple regression indicated that reduction in depression score and a reported history of sexual abuse were independently associated with improved tolerance to distension.

CONCLUSIONS: In patients with severe IBS, increased tolerance to rectal distension after psychological treatment is significantly associated with improved depression and reported sexual abuse. These results suggest that in some patients with severe IBS psychological rather than biological processes are primarily responsible for reduced tolerance to rectal distension.

Key Words: irritable bowel syndrome, • pain threshold, • psychological distress, • sexual abuse, • depression, • psycho-physiological disorders.

Abbreviations: IBS = irritable bowel syndrome;; HRSD = Hamilton depression score.

	INTRODUCTION

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Many patients with IBS have a lowered threshold to pain or discomfort during rectosigmoid distension (1–4). This reduced tolerance to rectal distension has been proposed as a biological marker for IBS (1,4), but this suggestion is not universally accepted (5–7). An alternative view suggests that IBS patients experience as painful, rectal sensations that healthy people would regard as nonpainful; this is thought to be part of their "hypervigilance" to bodily sensations (7,8). If this were so we would expect a lowered tolerance to rectal distension to be associated with numerous bodily symptoms and more general psychological distress.

Data from cross-sectional studies are conflicting in this respect (2,3,9–11). We have found that low tolerance to rectal distension is associated with complex psychiatric problems and reported prior sexual abuse in some patients but not others (12). In this study, we used a longitudinal design to test whether improvement in anxiety and depression is associated with a change in tolerance to rectal distension and whether reported sexual abuse influences such changes. No previous longitudinal studies have examined the relationship between improvement in rectal distension threshold and psychological symptoms with an adequate sample size (1,11,13).

We first performed a cross-sectional study in which we tested the hypothesis that baseline rectal distension threshold would be lower in people with 1) severe abdominal pain, 2) a reported history of sexual abuse, and 3) current psychiatric disorder. We also examined the relationship between psychological distress and low rectal distension threshold in those with and without a reported history of sexual abuse. Our main hypothesis was that improvement in abdominal pain and psychiatric symptoms after psychological treatment would be associated with increased tolerance to rectal distension and this would be greatest in those with a reported history of sexual abuse.

The subjects included in this study had been randomly allocated to psychotherapy, an antidepressant, or treatment as usual. We did not aim to compare the effects of these different treatments on rectal distension threshold, as numbers were so small. We did, however, control for the effects of treatment in our longitudinal analyses.

	MATERIALS AND METHODS

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Participants
The patients in this study were participating in a large randomized controlled trial comparing brief psychotherapy and an selective serotonin reuptake inhibitor antidepressant (paroxetine) with treatment as usual; the details have been described elsewhere (15). All patients fulfilled ROME I criteria for IBS (14), with symptoms for greater than 6 months, severe pain and no response to ‘usual’ medical treatment. The protocol used in the present study was introduced during the last 18 months of the trial, and 107 patients underwent the rectal distension protocol when they entered the trial (baseline); of these, 52 repeated the protocol after 3 months of treatment, and the remainder declined the post-treatment testing.

Assessments
Severity of abdominal pain on the day of assessment was recorded on a 0 to 100 visual analogue scale (16). Depressive and anxiety symptoms were assessed using the Hamilton rating scale for depression (HRSD) and SCL-90 (17,18). Psychiatric diagnosis was made using the Schedule for Clinical Assessment in Neuropsychiatry interview (15). A history of sexual abuse was recorded using a standardized questionnaire previously used in this population (19). "Reported sexual abuse" refers to patients who reported severe abuse (rape) and forced, unwanted touching of the genitalia; lesser degrees of abuse were categorized as no abuse.

Rectal Distension Protocol
We used a standardized technique previously described (20,21). In summary, the subject was first invited to defecate and then placed in the left lateral decubitus position with hips and knees bent. A thin-walled polyvinyl chloride bag (with a maximum capacity of 1200 ml) attached to a 4 mm catheter was inserted into the rectum and positioned so that the distal pole of the bag was 5 cm from the anal verge. A manometry port sited within the bag enabled the intrabag pressure to be recorded throughout the study.

Following intubation, a recovery period was allowed until the subjects reported no sensation of rectal distension, usually 10 to 15 minutes. A computer-driven, volume displacement device (Synectics Visceral Stimulator; Medtronic-Synectics, Stockholm, Sweden) was then used to inflate the bag. First, a 10-minute recording of rectal tone was made while the intrabag pressure was maintained as 10 mm Hg. The device was then set to automatically provide a series of inflation and deflation sequences according to a double random staircase protocol, which consists of two ascending staircases of inflation at a rate of 38 ml/s in 2-mm Hg steps. Recordings were made of intrabag pressure (mm Hg) and intrabag volume (ml) at each step.

For every inflation step, the patient was asked to describe the intensity of the sensation and to identify the onset of discomfort. When discomfort was reported, the system was switched to a tracking mode in which subsequent inflation steps would either be the same or 2 mm Hg lower than the stimulus that generated the discomfort. Two random sequences of inflation were followed. The system switched between these staircases in random fashion throughout the procedure. When three discomfort thresholds had been acquired in each of the two staircases, the system automatically stopped the procedure.

The median values of pressure and volume during the last 10 seconds of each of the three distensions that caused discomfort in each staircase were used for analysis.

Ethics committee approval was obtained from each relevant Health Authority, and all patients signed written consent to participate in the study after full verbal explanation and provision of written information.

Statistical Analyses
Rectal distension thresholds were not normally distributed in the cross-sectional analysis of baseline data, so their relationship with other variables used the Mann-Whitney test and Spearman correlation coefficient. The analysis was performed separately for patients with and without a reported history of sexual abuse.

Change in rectal distension thresholds (follow-up threshold subtracted from baseline threshold) in the longitudinal analysis were normally distributed, so comparison with changes in abdominal pain and psychological scores used partial correlation coefficient with treatment group, baseline values of rectal distension threshold, abdominal pain, and psychological scores as covariates (40 people completed all these measures at baseline and at follow-up). Comparison of people with and without reported sexual abuse used ANCOVA with treatment group and baseline rectal distension values as covariates.

We controlled for baseline rectal distension threshold because change in this value (after 3 months of psychotherapy, antidepressant, or treatment as usual) was significantly associated with baseline value (ie, the lowest baseline thresholds had greatest scope for change). We also controlled for treatment because reduction in rectal distension threshold was slightly, though not significantly greater in the group treated with paroxetine (p = .23).

We found that changes in abdominal pain, changes in psychological scores, and a history of sexual abuse were all associated with change in volume threshold; therefore, a multiple regression analysis was performed to identify the variables most closely associated with change in volume threshold between baseline and follow-up. This analysis included as independent variables entered together: age, sex, a reported history of sexual abuse, treatment group, pretreatment volume threshold, change in abdominal pain, and change in HRSD.

	RESULTS

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The characteristics of the patients included in this study were very similar to the 257 participants included in the whole trial (15). The median age was 45 years (range, 19 to 63 years), and half the patients had suffered IBS for 10 years or more. Forty-three (83%) were female, 36 (69%) were married or cohabiting, and 15 (29%) were unemployed because of ill health. Forty-four percent had a psychiatric disorder, and 21% reported sexual abuse. Of the 52 subjects tested before and after treatment, 20 had been randomly allocated to receive paroxetine, 19 received brief psychotherapy, and 13 were allocated to the treatment as usual group. There were no significant differences between the 52 subjects tested twice and the 55 who were only tested once with respect to age, sex, years of education, experience of abuse, severity of depression, pain and other IBS symptoms, initial volume, and pressure measurements.

Tolerance to Rectal Distension Before Treatment
In the 107 patients assessed at baseline, there were no significant associations between rectal distension threshold (volume or pressure) with age, sex, abdominal pain, or SCL90 scores, except distension threshold (volume) was correlated with SCL-90 somatization score (r = 0.22, p = .024).

Lower rectal distension thresholds were found in the 14 patients with panic disorder (median and interquartile range: 42.1 [IQR = 35 to 67] compared with 79.3 [46 to 138] for the remainder, z = –2.10, p = .036) and in 41 patients with neurasthenia (60.5 [IQR = 36 to 89] vs. 87.4 [51 to 147], z = –2.05, p = .04) but not in other psychiatric disorders.

One hundred and three subjects completed all measures. Among the 78 patients who had not reported sexual abuse, correlations between rectal distension thresholds and psychological scores at baseline were very low, and none approached significance (Table 1). By contrast, most of the psychological symptom scores in the 25 patients who reported sexual abuse showed moderate correlations with the rectal distension thresholds, and three of these values reached statistical significance (Table 1).

Of the 11 patients who had reported sexual abuse, 5 received psychotherapy; the increase in volume threshold was 54.1 ml (SEM = 14.2); this compares with an increase of 27.2 ml (SEM = 15.2) for the 5 patients receiving paroxetine and a decrease in volume threshold for the one patient who received treatment as usual of 85.7 ml (p = .017). Among the patients without reported sexual abuse, there was an increase in volume threshold (15.4 [SEM = 8.6]) only for the 15 patients receiving paroxetine; this compares with a decrease of 22.7 [SEM = 8.9] in the 14 patients receiving psychotherapy and 9.2 [SEM = 9.7] in the 12 patients receiving treatment as usual (p = .013).

Multiple Regression Analysis
In the multiple regression analysis to predict change in volume threshold, two variables were included in the final model: HRSD and reported history of sexual abuse, which together predicted 24.4% of the variance (Table 3).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

In relation to our main hypothesis, we found that improvement in depression, but not abdominal pain, was significantly associated with increased rectal distension threshold volume. The increase in rectal distension threshold volume was also associated with a reported history of sexual abuse, which made an independent contribution to the change in rectal distension threshold. There may have been a direct effect of paroxetine on volume perception threshold among the patients without reported sexual abuse.

Our findings broaden the concept of lowered rectal distension threshold as a "biological marker" of IBS. We suggest that, at least in some patients, reduced tolerance to rectal distension is likely to be due to perceptual response bias (8). Whitehead et al. (8) demonstrated that, among women who did not have IBS, those who reported prior sexual abuse had lower pain thresholds to distension than non-abused women, suggesting that reduced tolerance to rectal distension might not be specific to IBS.

Our findings also concur with those of Naliboff et al. (9), who reported two groups of IBS patients with lowered rectal tolerance, one with true hypersensitivity and the other who were hypervigilant for rectal stimuli (9). It would be helpful in future studies to search for biological processes in those with true hypersensitivity and understand more fully the psychological processes in the hypervigilant group. These processes may overlap, but our sample may have been too small and selected to adequately study the direct correlation of reported abdominal pain and distension threshold (true hypersensitivity), which is a feature of many IBS patients. Although reported sexual abuse and current depression might be related to hypervigilance these occur in a minority of IBS patients.

We found very marked changes in rectal distension threshold in the small number of patients who reported prior sexual abuse and who received psychotherapy; these changes are associated with marked improvements in health-related quality of life, as previously reported (15). This finding is compatible with the suggestion that sexual abuse is associated with marked hypervigilance that is modified when people are helped by psychotherapy. Although others have not found clear evidence of a direct effect of paroxetine on the gut (22), our data suggest this does occur in patients without reported sexual abuse, although our numbers were too small to test this adequately (13).

The main strength of this study is its longitudinal design, in which each patient acts as their own control, thereby reducing the intersubject variation, which is considerable in rectal distension studies (6). Our study included sufficient numbers to control for treatment group and baseline thresholds, often absent in previous studies. Potential weaknesses of this study include the limited number of subjects, which prevented proper analysis of each treatment group separately, and the selection of patients with severe and chronic IBS, so the results cannot be generalized to all IBS patients. Like Whitehead et al., we found that the association between depression and rectal tolerance was more evident for volume than pressure. This is likely to reflect the fact that intensity of sensation from the rectum is determined primarily by stretch rather than tension (23).

In conclusion, our results suggest that changes in depression are associated with changes in "response bias," ie, a reduction in the tendency to focus on bodily symptoms, and such changes were greatest in those who reported a history of sexual abuse. If lowered tolerance to rectal distension is to be regarded as a "biological marker" for IBS, this concept needs to embrace psychological mechanisms as well as other causes of change in pain threshold.

	ACKNOWLEDGMENTS

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Grant support Medical Research Council (MRC) of UK financed the study. The North Western Region Health Authority (UK) R& D Directorate financed the psychotherapists. SKB provided the paroxetine but was not involved in the design, conduct, or analysis of the trial.

We thank Hans Gregersen for his helpful comments about the manuscript.

Received for publication January 8, 2004.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 

1. Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 1995; 109: 40–52.[CrossRef][Medline]
2. Whitehead WE, Holtkotter B, Enck P, Hoelzl R, Holmes KD, Anthony J, Shabsin HS, Schuster MM. Tolerance for rectosigmoid distension in irritable bowel syndrome. Gastroenterology 1990; 98: 1187–92.[Medline]
3. Prior A, Sorial E, Sun W-m, Read NW. Irritable bowel syndrome: differences between patients who show rectal sensitivity and those who do not. Eur J Gastroenterol Hepatol 1993; 5: 343–9.
4. Bouin M, Plourde V, Boivin M, Riberdy M, Lupien F, Laganiere M, Verrier P, Poitras P. Rectal distension testing in patients with irritable bowel syndrome: sensitivity, specificity and predictive values of pain sensory thresholds. Gastroenterology 2002; 122: 1771–7.[CrossRef][Medline]
5. Zighelboim J, Talley NJ, Phillips SF, Harmsen WS, Zinsmeister AR. Visceral perception in irritable bowel syndrome. Dig Dis Sci 1995; 40: 819–27.[CrossRef][Medline]
6. Kendall GP, Thompson DG, Day SJ, Lennard-Jones JE. Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. Gut 1990; 31: 1062–8.[Abstract/Free Full Text]
7. Whitehead WE, Palsson OS. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception. Gastroenterology 1998; 115: 1263–7.[CrossRef][Medline]
8. Whitehead WE, Crowell MD, Davidoff AL, Palsson OS, Schuster MM. Pain from rectal distension in women with irritable bowel syndrome: relationship to sexual abuse. Dig Dis Sci 1997; 42: 796–804.[CrossRef][Medline]
9. Naliboff BD, Munakata J, Fullerton S, Gracely RH, Kodner A, Harraf F, Mayer EA. Evidence for two distinct perceptual alterations in irritable bowel syndrome. Gut 1997; 41: 505–12.[Abstract/Free Full Text]
10. Munakata J, Naliboff B, Harraf F, Kodner A, Lembo T, Chang L, Silverman DHS, Mayer EA. Repetitive sigmoid colon stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. Gastroenterology 1997; 112: 55–63.[CrossRef][Medline]
11. Prior A, Colgan SM, Whorwell PJ. Changes in rectal sensitivity after hypnotherapy in patients with irritable bowel syndrome. Gut 1990; 31: 896–8.[Abstract/Free Full Text]
12. Guthrie E, Creed FH, Fernandes L Fernandes , Ratcliffe J, Van der Jagt J, Martin J, Howlett S, Read NW, Barlow J, Thompson D Tomenson B. Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome. Gut 2003; 52: 1626–22.
13. Poitras P, Poitras MR, Plourde V, Boivin M, Verrier P. Evolution of visceral sensitivity in patients with irritable bowel syndrome. Dig Dis Sci 2002; 47: 914–20.[CrossRef][Medline]
14. Thompson WG, Creed F, Drossman DA, Heaton KW, Mazzacca G. Functional bowel disease and functional abdominal pain. Gastroenterology International 1992; 5: 75–91.
15. Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B. The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 2003; 124: 303–17.[CrossRef][Medline]
16. Drossman DA, Li Z, Toner BB, Diamant NE, Creed FH, Thompson D, Read NW, Babbs C, Barreiro M, Bank L. Functional bowel disorders. A multicenter comparison of health status and development of illness severity index. Dig Dis Sci 1995; 40: 986–95.[CrossRef][Medline]
17. Derogatis LR. SCL-90-R administration, scoring, procedures manual II for the revised version. 2nd ed. Towson, MD: Clinical Psychometric Research; 1983.
18. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiat 1960; 23: 56–62.
19. Drossman DA, Leserman J, Nachman G, Li ZM, Gluck H, Toomey TC, Mitchell CM. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Int Med 1990; 113: 828–33.
20. Whitehead WE, Delvaux M. Standardization of barostat procedures for testing smooth muscle tone and sensory thresholds in the gastrointestinal tract. The Working Team of Glaxo-Wellcome Research, UK. Dig Dis Sci 1997; 42: 223–41.[CrossRef][Medline]
21. Sun WM, Read NW, Prior A, Daly JA, Cheah SK, Grundy D. Sensory and motor responses to rectal distension vary according to the rate and pattern of balloon distension. Gastroenterology 1990; 99: 1008–15.[Medline]
22. Kuiken SD, Tytgat GNJ, Boeckxstaens GEE. The selective serotonin inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomised placebo-controlled study. Clin Gastroenterol Hepatol 2003; 1: 219–28.[CrossRef][Medline]
23. Petersen P, Gao C, Arendt-Nielsen L, Gregersen H, Drewes AM. Pain intensity and biomechanical responses during ramp-controlled distension of the human rectum. Dig Dis Sci 2003; 48: 1310–6.[CrossRef][Medline]

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