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General introduction 21 1 channels are involved in the propagation and processing of abdominal pain signals in IBS. In chapter 4 , we reviewed current insights regarding TRP channels and their potential implications for treatment in IBS. As human data on the functional relevance of the TRPM8 channel is exceptionally limited, we investigated neuro-immune interactions in the human gut to elucidate the role of TRPM8 in nociceptive processes and gut health in chapter 5 . Peppermint oil is a potent TRPM8 agonist and has been shown to ameliorate abdominal pain in IBS in prior studies. Most of these studies, however, suffered from methodological flaws or were conducted in small populations. In chapter 6 , we assessed the pharmacokinetic profile of a newly developed ileocolonic release peppermint oil capsule in healthy volunteers. This formulation was produced to decrease upper GI adverse events associated with conventional, small-intestinal release peppermint oil and to increase efficacy by the enhancement of local colonic anti- nociception. Following the pharmacokinetic pilot study, we investigated the efficacy and safety of small-intestinal and ileocolonic release peppermint oil in a Rome IV IBS population in a randomized, placebo-controlled trial (RCT) with a highly qualitive experimental design. The results of this RCT have been described in chapter 7 . Since IBS is associated with high healthcare related costs, it is increasingly important that therapeutic entities are also cost-effective. Therefore, in chapter 8 , we determined the cost-effectives of peppermint oil alongside the previously mentioned RCT. Due to the lack of validated biomarkers, end-of-day symptom diaries are important to assess treatment response in patients with IBS. The validity and reliability of paper diaries, however, is impeded by fake adherence and recall bias. Given that an accurate assessment of treatment response in RCTs is essential in the search for better treatments for patients with IBS, we implemented a framework for a digitalized data collection in our previously mentioned peppermint oil RCT. In chapter 9 , we describe the smartphone application that was used as a digital symptom diary in addition to the overall data collection method. Furthermore, we assessed patient’ adherence to the digital diary and investigated how patient characteristics associate with adherence. Finally, in chapter 10 , we summarize the main findings of this thesis, and discuss implications for future research in this area and everyday clinical practice.