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Chapter 5 106 modulating release of TNF- ܤ and IL-10. 12 Human data on the role of intestinal TRPM8 is limited to a single study showing upregulation of TRPM8 mRNA in biopsies from Crohn’s disease patients, in both inflamed and non-inflamed mucosa. 14 In IBS, a single brief report describes an association of TRPM8 gene polymorphism with colonic transit. 15 Collectively, these studies show that there is a potential role for TRPM8- mediated reduction of gut symptoms. We sought to shed light on the putative role of TRPM8 in IBS. We hypothesized, in line with findings from previous animal studies, that TRPM8 has an anti-inflammatory effect and by this virtue represents a key factor in the pathophysiology of IBS. Materials and methods Patient population IBS patients (age 18-75 years) were recruited from 2 centres: the Maastricht University Medical Center+ (MUMC), The Netherlands, and The Royal London Hospital, in London, UK. Medical history was taken by a (trainee) gastroenterologist or research nurse, and if indicated, abdominal imaging and/or blood, fecal analyses were performed to exclude organic disease. A history of abdominal surgery, except for uncomplicated appendectomy, cholecystectomy, or hysterectomy, was reason for exclusion. The diagnosis of IBS was confirmed based on the Rome III criteria by an investigator independent from the treating physician. Healthy controls for the Maastricht cohort were recruited from the general population using advertisements. Controls from the London cohort were attending the Endoscopy unit for anaemia investigation and did not have macroscopic inflammation or any organic abnormality other than polyps and/or hemorrhoids. Controls from both the Maastricht and London cohort were requested to complete the Rome III questionnaire to rule out the presence of IBS. Demographic characteristics of all study patients are presented in Table 5.1 . The study protocols had been approved by the respective local Ethics Committees, and all study procedures were performed in compliance with Good Clinical Practice Guidelines and according to the revised Declaration of Helsinki. All subjects gave a written informed consent prior to participation.