Zsa Zsa Weerts

Addendum 254 symptomatology, psychological comorbidities and lower quality of life. This implies that results from Rome III IBS studies may not be directly transferable to Rome IV IBS populations. In clinic however, both groups should be considered as having IBS. Besides variations in population characteristics due to different diagnostic criteria used, symptoms within patients are also know to vary over time. Given that insight in factors affecting the natural disease course can help in the search for new patient-tailored targeted treatment strategies, we evaluated symptom evolution and characteristics that could predict the disease course over a five-year follow up period in chapter 3 . Of 161 Rome III IBS patients of the Maastricht IBS cohort, 30% did not fulfill the Rome III criteria any longer and had significantly lower levels of GI symptoms and GI-specific anxiety after five years follow-up. Nevertheless, comorbid anxiety and depression and quality of life were comparable between patients that did and did no longer fulfill the diagnostic criteria at follow-up. No baseline predictors for being Rome-IV positive at follow-up were found. These results suggest that long-term quality of life and general wellbeing might depend on concurrent psychological symptoms, rather than GI symptom improvement over time. Therefore, therapeutic efforts should also be aimed at addressing mental health issues. Part II - Transient receptor potential channels as therapeutic target Although the number of therapeutic options for IBS has grown in the last decades, treatment of abdominal pain in particular remains challenging and is often unsatisfactory. In the search for cost-effective treatments, Transient Receptor Potential (TRP) channels are promising targets for therapeutic interventions. TRP channels are known to have temperature-sensing properties, among many other functions. Growing evidence indicates that TRP channels in the GI tract are involved in the propagation and processing of abdominal pain signals in IBS. To gain an overview of current knowledge on the role of various TRP channels in visceral nociceptive processes in IBS, we first performed an extensive literature search and summarized the findings in chapter 4 . An extensive overview of knowledge on TRPV1, TRPV4, TRPA1, TRPM8 and their potential implications for treatment in IBS was given. Of these, TRPV1 is most widely-studied and its stimulation is associated with increased visceral nociception, hypersensitivity and increased neurogenic inflammation. Although direct antagonism of TRPV1 led to excellent analgesia, safety issues impair its clinical use. Knowledge regarding another important channel, the TRPM8 channel, is mostly derived from animal studies. These have shown that TRPM8 appears to have an