Visceral Hypersensitivity in Irritable Bowel Syndrome: Does It Really Normalize Over Time?

Abstract

We would like to comment on the article by Naliboff et al1Naliboff B.D. Berman S. Suyenobu B. Labus J.S. Chang L. Stains J. Mandelkern M.A. Mayer E.A. Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients.Gastroenterology. 2006; 131: 352-365Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar published in the August 2006 issue of Gastroenterology. Hypersensitivity of the colon is often considered as a biological marker of irritable bowel syndrome (IBS) in many of these patients.2Mertz H. Naliboff B. Munakata J. Niazi N. Mayer E.A. Altered rectal perception is a biological marker of patients with irritable bowel syndrome.Gastroenterology. 1995; 109: 40-52Abstract Full Text PDF PubMed Scopus (897) Google Scholar, 3Bouin M. Plourde V. Boivin M. Riberdy M. Lupien F. Laganiere M. Verrier P. Poitras P. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds.Gastroenterology. 2002; 122: 1771-1777Abstract Full Text Full Text PDF PubMed Scopus (409) Google Scholar, 4Faure C, Wieckowska A. Somatic referral of visceral sensations and rectal sensory threshold for pain in children with functional gastrointestinal disorders. J Pediatr (in press).Google Scholar The causes and consequences of this process are still debated, and data are obviously lacking on the natural history of this hypersensitivity. Naliboff et al1Naliboff B.D. Berman S. Suyenobu B. Labus J.S. Chang L. Stains J. Mandelkern M.A. Mayer E.A. Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients.Gastroenterology. 2006; 131: 352-365Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar realized a tour de force when they studied the pain threshold to rectal balloon distention in IBS patients every 4 months during 1 year. The information provided here is unique and essential. The authors observed that:1IBS symptoms remained stable over 12 months, whereas visceral hypersensitivity improved, suggesting an absence of direct relationship between both phenomena, and confirming the notion extrapolated from other studies where clinical improvement could be obtained by psychological5Poitras P. Riberdy Poitras M. Plourde V. Boivin M. Verrier P. Evolution of visceral sensitivity in patients with irritable bowel syndrome.Dig Dis Sci. 2002; 47: 914-920Crossref PubMed Scopus (89) Google Scholar or pharmacologic6Kuiken S.D. Tytgat G.N. Boeckxstaens G.E. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.Clin Gastroenterol Hepatol. 2003; 1: 219-228Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar, 7Tack J. Broekaert D. Fischler B. Van Oudenhove L. Gevers A. Janssens J. A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.Gut. 2006; 55: 1095-1103Crossref PubMed Scopus (249) Google Scholar treatments, without modification of intestinal sensitivity.2The measure of visceral sensitivity remained stable over 4 months, an important confirmation of other studies,5Poitras P. Riberdy Poitras M. Plourde V. Boivin M. Verrier P. Evolution of visceral sensitivity in patients with irritable bowel syndrome.Dig Dis Sci. 2002; 47: 914-920Crossref PubMed Scopus (89) Google Scholar, 6Kuiken S.D. Tytgat G.N. Boeckxstaens G.E. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.Clin Gastroenterol Hepatol. 2003; 1: 219-228Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar, 7Tack J. Broekaert D. Fischler B. Van Oudenhove L. Gevers A. Janssens J. A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.Gut. 2006; 55: 1095-1103Crossref PubMed Scopus (249) Google Scholar often using a 10- to 14-week comparison period.3At the 3rd and 4th barostat testing, done at 8 and 12 months, respectively), the pain threshold of the 20 IBS patients increased significantly (real values not given in the text but were extrapolated from figures) from ≈30 mm Hg to ≈36 mm Hg (the normal range being ≈34–44 mm Hg).We absolutely agree with the authors that this increase in the pain threshold probably reflects a process of habituation (although definitive proof is indeed still lacking). However, we believe that this habituation process is not restricted to IBS. As the authors mention, a definite trend (P > .1) was noted; the mean discomfort threshold in their 12 healthy control subjects increased over time from ≈35–36 mm Hg to ≈42–43 mm Hg. It is striking to see in Figure 2 in the article that the longitudinal changes in discomfort thresholds revealed absolute parallel curves for IBS patients and for healthy controls, clearly suggesting that both groups had a similar evolution. Such an increase in visceral pain thresholds has been already described in healthy controls submitted to repeated distentions of the esophagus.8Worthen S.F. Hanisen J. Aziz Q. Hobson A.R. Effect of anxiety on the sensory and perceptual characteristics of visceral and somatic sensation.Gut. 2005; 54: A19Google Scholar Consequently, if we can appreciate the increase in the measured pain threshold with repeated testing, we are not convinced that “visceral hypersensitivity normalized over time” as the authors said. In Figure 2, the distribution of normal controls cannot follow the hatched area extrapolated from the initial test, but must be adjusted for the control values obtained at 0, 4, 8, and 12 months specifically. The manuscript report did not allow us to perform statistical analyses, but the discomfort thresholds at each time point seem always lower in IBS patients than in the control subjects, the difference between IBS patients and controls being thus stable over time.In our opinion, this most interesting paper therefore shows that visceral hypersensitivity is (1) present in IBS patients, (2) stable over a 4-month period, and (3) persistent over a longer period of 8–12 months (although the discomfort thresholds can vary over time). We would like to comment on the article by Naliboff et al1Naliboff B.D. Berman S. Suyenobu B. Labus J.S. Chang L. Stains J. Mandelkern M.A. Mayer E.A. Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients.Gastroenterology. 2006; 131: 352-365Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar published in the August 2006 issue of Gastroenterology. Hypersensitivity of the colon is often considered as a biological marker of irritable bowel syndrome (IBS) in many of these patients.2Mertz H. Naliboff B. Munakata J. Niazi N. Mayer E.A. Altered rectal perception is a biological marker of patients with irritable bowel syndrome.Gastroenterology. 1995; 109: 40-52Abstract Full Text PDF PubMed Scopus (897) Google Scholar, 3Bouin M. Plourde V. Boivin M. Riberdy M. Lupien F. Laganiere M. Verrier P. Poitras P. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds.Gastroenterology. 2002; 122: 1771-1777Abstract Full Text Full Text PDF PubMed Scopus (409) Google Scholar, 4Faure C, Wieckowska A. Somatic referral of visceral sensations and rectal sensory threshold for pain in children with functional gastrointestinal disorders. J Pediatr (in press).Google Scholar The causes and consequences of this process are still debated, and data are obviously lacking on the natural history of this hypersensitivity. Naliboff et al1Naliboff B.D. Berman S. Suyenobu B. Labus J.S. Chang L. Stains J. Mandelkern M.A. Mayer E.A. Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients.Gastroenterology. 2006; 131: 352-365Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar realized a tour de force when they studied the pain threshold to rectal balloon distention in IBS patients every 4 months during 1 year. The information provided here is unique and essential. The authors observed that:1IBS symptoms remained stable over 12 months, whereas visceral hypersensitivity improved, suggesting an absence of direct relationship between both phenomena, and confirming the notion extrapolated from other studies where clinical improvement could be obtained by psychological5Poitras P. Riberdy Poitras M. Plourde V. Boivin M. Verrier P. Evolution of visceral sensitivity in patients with irritable bowel syndrome.Dig Dis Sci. 2002; 47: 914-920Crossref PubMed Scopus (89) Google Scholar or pharmacologic6Kuiken S.D. Tytgat G.N. Boeckxstaens G.E. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.Clin Gastroenterol Hepatol. 2003; 1: 219-228Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar, 7Tack J. Broekaert D. Fischler B. Van Oudenhove L. Gevers A. Janssens J. A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.Gut. 2006; 55: 1095-1103Crossref PubMed Scopus (249) Google Scholar treatments, without modification of intestinal sensitivity.2The measure of visceral sensitivity remained stable over 4 months, an important confirmation of other studies,5Poitras P. Riberdy Poitras M. Plourde V. Boivin M. Verrier P. Evolution of visceral sensitivity in patients with irritable bowel syndrome.Dig Dis Sci. 2002; 47: 914-920Crossref PubMed Scopus (89) Google Scholar, 6Kuiken S.D. Tytgat G.N. Boeckxstaens G.E. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.Clin Gastroenterol Hepatol. 2003; 1: 219-228Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar, 7Tack J. Broekaert D. Fischler B. Van Oudenhove L. Gevers A. Janssens J. A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.Gut. 2006; 55: 1095-1103Crossref PubMed Scopus (249) Google Scholar often using a 10- to 14-week comparison period.3At the 3rd and 4th barostat testing, done at 8 and 12 months, respectively), the pain threshold of the 20 IBS patients increased significantly (real values not given in the text but were extrapolated from figures) from ≈30 mm Hg to ≈36 mm Hg (the normal range being ≈34–44 mm Hg). We absolutely agree with the authors that this increase in the pain threshold probably reflects a process of habituation (although definitive proof is indeed still lacking). However, we believe that this habituation process is not restricted to IBS. As the authors mention, a definite trend (P > .1) was noted; the mean discomfort threshold in their 12 healthy control subjects increased over time from ≈35–36 mm Hg to ≈42–43 mm Hg. It is striking to see in Figure 2 in the article that the longitudinal changes in discomfort thresholds revealed absolute parallel curves for IBS patients and for healthy controls, clearly suggesting that both groups had a similar evolution. Such an increase in visceral pain thresholds has been already described in healthy controls submitted to repeated distentions of the esophagus.8Worthen S.F. Hanisen J. Aziz Q. Hobson A.R. Effect of anxiety on the sensory and perceptual characteristics of visceral and somatic sensation.Gut. 2005; 54: A19Google Scholar Consequently, if we can appreciate the increase in the measured pain threshold with repeated testing, we are not convinced that “visceral hypersensitivity normalized over time” as the authors said. In Figure 2, the distribution of normal controls cannot follow the hatched area extrapolated from the initial test, but must be adjusted for the control values obtained at 0, 4, 8, and 12 months specifically. The manuscript report did not allow us to perform statistical analyses, but the discomfort thresholds at each time point seem always lower in IBS patients than in the control subjects, the difference between IBS patients and controls being thus stable over time. In our opinion, this most interesting paper therefore shows that visceral hypersensitivity is (1) present in IBS patients, (2) stable over a 4-month period, and (3) persistent over a longer period of 8–12 months (although the discomfort thresholds can vary over time). Longitudinal Change in Perceptual and Brain Activation Response to Visceral Stimuli in Irritable Bowel Syndrome PatientsGastroenterologyVol. 131Issue 2PreviewBackground & Aims: Symptom-related fears and associated hypervigilance toward visceral stimuli may play a role in central pain amplification and irritable bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to decreased salience of threat and reduction of hypervigilance. We sought to evaluate hypervigilance in IBS visceral hypersensitivity and associated brain activity. Methods: Twenty IBS patients (14 female; moderate to severe symptoms) and 14 healthy controls participated in symptom and rectal distention assessments 6 times over 12 months. Full-Text PDF ReplyGastroenterologyVol. 132Issue 1PreviewWe appreciate the comments of Dr Faure and colleagues on our manuscript entitled “Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients.”1 They point out that the change in visceral perception over the course of the multiple testings observed in the patients with irritable bowel syndrome (IBS) may also occur in the control subjects, suggesting that the group differences in perceptual sensitivity would therefore remain constant despite the changes for both groups. Full-Text PDF