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Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts
  1. Magnus Simrén1,2,
  2. Hans Törnblom1,
  3. Olafur S Palsson2,
  4. Miranda A L van Tilburg2,
  5. Lukas Van Oudenhove3,
  6. Jan Tack3,
  7. William E Whitehead2
  1. 1 Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. 2 Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  3. 3 Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
  1. Correspondence to Professor Magnus Simrén, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden; magnus.simren{at}


Objective Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms.

Design We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression.

Results In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047–0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05).

Conclusions A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.


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  • Contributors Inclusion of patients and critical revision of manuscript: all co-authors. Statistical analyses: MS and LVO. Manuscript draft: MS. Obtained funding: MS, JT and WEW.

  • Funding This study was supported by NIDDK (grant RO1 DK31369), the Swedish Medical Research Council (grants 13409, 21691 and 21692), AFA Insurance, unrestricted grants from Ferring Pharmaceuticals and Danone Research, and by the Faculty of Medicine, University of Gothenburg. LVO is a Research Professor funded by the KU Leuven Special Research Fund (Bijzonder Onderzoeksfonds, BOF).

  • Competing interests MS has received unrestricted research grants from Danone, and Ferring Pharmaceuticals, and served as a Consultant/Advisory Board member for AstraZeneca, Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire, and as a speaker for Tillotts, Takeda, Shire and Almirall. HT has served as Consultant/Advisory Board member for Almirall, Danone and Shire. MALvT has obtained research support from Takeda for investigator initiated study. OSP has received salary support from a research grants from Takeda Pharmaceuticals and Salix Pharmaceuticals and from a consulting agreement with Ironwood Pharmaceuticals and an educational grant provided by Takeda Pharmaceuticals, and received a speaker honorarium in an educational programme supported by Ironwood Pharmaceuticals and Takeda Pharmaceuticals. JT has given scientific advice to Almirall, AstraZeneca, Danone, Menarini, Novartis, Nycomed, Ocera, Ono pharma, Shire, SK Life Sciences, Theravance, Tranzyme, Xenoport, and Zeria Pharmaceuticals, and has been member of the Speaker bureau for: Abbott, Almirall, AlfaWasserman, AstraZeneca, Janssen, Menarini, Novartis, Nycomed, Shire, Zeria. WEW received research grants from Takeda, Ironwood, Salix, and the Rome Foundation; served as a consultant to Biomerica USA, Ono Pharmaceuticals and Ferring; and received unrestricted educational grants from Takeda and Ferring.

  • Patient consent Obtained.

  • Ethics approval Regional Ethical Review Boards in Chapel Hill, Gothenburg or Leuven.

  • Provenance and peer review Not commissioned; externally peer reviewed.