Pain severity correlates with biopsy mediated colonic afferent activation but not psychological scores in IBS-D patients

Objectives: Despite heterogeneity an increased prevalence of psychological co-morbidity and an altered pro-nociceptive gut microenvironment have repeatedly emerged as causative pathophysiology in patients with irritable bowel syndrome(IBS). Our aim was to study these phenomenaby comparing gut related symptoms, psychological scores and biopsy samples generated from a detailed diarrhoea predominant IBS patient (IBS-D) cohort prior to their entry into a previously reported clinical trial. Methods: Data was generated from 42 IBS-D patients who completed a daily 2 week bowel symptom diary, the Hospital Anxiety and Depression score,the Patient Health Questionnaire-12 Somatic Symptom score and underwent unprepared flexible sigmoidoscopy. Sigmoid mucosal biopsies were separately evaluated using immunohistochemistry and culture supernatants to determine cellularity, mediator levels and ability to stimulate colonic afferent activity.Results: Pain severity scores significantly correlated with the daily duration of pain(r=0.67, p[less than] 0.00001),urgency (r=0.57, p [less than] 0.0005) and bloating (r=0.39, p [less than] 0.05)but not psychological symptom scores for anxiety, depression or somatisation. Furthermore,pain severity scores from individual IBS-D patients were significantly correlated (r=0.40, p[less than] 0.008) with stimulation of colonic afferent activation mediated by their biopsysupernatant but not with biopsy cell counts nor measured mediator levels. Discussion: Peripheral pro-nociceptive changes in the bowel appear more important than psychological factors in determining pain severity within a tightly phenotyped cohort of IBS-D patients. No individual mediator was identified as the cause of this pro-nociceptive change