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Chapter 1 16 abdominal pain perception. In the 1990s, several research groups further investigated the brain-gut interactions by using functional Magnetic Resonance Imaging (fMRI) and positron emission tomography (PET). 67 These studies were important to elucidate brain areas and networks associated with visceral pain in healthy and disordered states, such as IBS. Since then, several studies have examined the complex role of the autonomic nervous system by applying a mechanical or thermal intestinal stimulus during fMRI. They demonstrated that painful rectal balloon distensions resulted in activation of various brain areas 68 ; the primary and secondary somatosensory cortex, insula, cingulate cortex, prefrontal cortexes, and thalamus. 67,69-72 In addition, it was shown that individual factors such as coping mechanisms, depression, anxiety, cognitions, and emotions can bi-directionally modulate cortical, limbic, and brainstem nuclei. This can subsequently result in either amplification or subordination of noxious stimuli in healthy volunteers and IBS patients and thereby determines whether noxious stimuli are perceived as painful. 73 When compared to healthy controls, patients with IBS appeared to have different activation patterns of brain areas involved (in visceral pain processing and modulation). 71,74 Moreover, there are indications that the vagal efferent arm exhibits downward modulatory properties and can even affect low grade inflammation. Several studies have indicated that this efferent vagal activity can be impaired in IBS. 42,43 Altogether, these findings point to increased facilitation and/or decreased inhibition of pain signals in IBS. 73,75 In combination with peripheral alterations, this can contribute to abdominal pain. Further research is needed to investigate how all factors interact and why they lead to symptoms in some, but not all patients with IBS. Treatment of IBS Currently, there is no effective cure for IBS. Available treatment modalities merely aim at symptom amelioration and mostly benefit only subgroups of patients. Regardless of the treatment chosen, pivotal for treatment success are a good patient-physician relationship and a timely discussion about treatment expectations. 20 Furthermore, as many psychiatric and extra-intestinal comorbidities interfere with patients’ symptom severity as well as daily functioning, constructing a multidimensional clinical profile and assessing all factors that impede QoL, are needed to choose a patient-centered approach. 76 Traditionally, treatment starts with reassurance and explaining the disorder. For a subgroup of patients with mild symptoms, this is sufficient and no further treatment is required. 76 Given that a large proportion of patients report their symptoms to be triggered by meals or specific foods 57 , dietary and lifestyle modifications can also relief