Hersenmechanismen en neurotransmittersystemen van viscerale nociceptie en tolerantie van normale maaltijdvolumes in gezonde vrijwilligers en functionele dyspepsie

One of the most common functional gastrointestinal disorders, functional dyspepsia (FD) is defined as the presence of recurrent or chronic epigastric symptoms in the absence of underlying organic abnormalities likely to explain them. The four cardinal symptoms of FD are epigastric pain, epigastric burning, early satiety and postprandial fullness. Furthermore, FD patients are characterized by abnormal regional cerebral activity (during rest and (anticipated) visceral pain) and structural changes in the brain, but it is unknown which neurotransmitter systems are involved. In addition, FD patients often report impaired meal volume tolerance, which together with enhanced visceral pain perception might lead to unexplained weight loss, an important feature of FD patients, especially in tertiary care. However, even in healthy individuals, very little is known about the mechanisms required for the tolerance of normal meal volumes without inducing epigastric symptoms. Despite being intensively investigated, the etiology and pathogenesis of FD remain incompletely understood. However, there is growing consensus that disturbances of the interactions between the brain and the digestive system, which can occur at any level, play a major role the generation of dyspeptic symptoms. The “brain-gut axis” provides the neurobiological basis of these interactions and constitutes an important part of an integrated interoceptive system through which homeostatic information about the body’s physiological condition is continuously conveyed to the brain through neural, hormonal and/or immune signalling pathways. At the brain level, the processing of this interoceptive homeostatic-afferent information is modulated by signals from exteroceptive (visual, olfactory) sensory modalities, affective and cognitive processes as well as inputs from the brain reward system, resulting in appropriate autonomic and/or behavioural responses. The general aim of this work was to elucidate the central mechanisms and neurotransmitter systems involved in visceral pain perception and meal volume tolerance in health as well as in FD. This doctoral research project aimed to elucidate the central mechanisms and neurotransmitter systems involved in visceral pain perception and meal volume tolerance in health as well as in Functional Dyspepsia (FD). The following research questions were investigated:1. Are endogenous opioids involved in visceral pain processing in healthy subjects?2. Is the endocannabinoid system involved in the altered visceral pain perception and dysregulation of meal volume tolerance and food intake reported in FD patients?3. Are brain response patterns during gastric distension induced by nutrient infusion different from responses to gastric balloon distension due to the different composition of the stimuli inducing differential gut hormones responses?To address these questions three functional neuroimaging studies were performed, each of which constitutes one part of this thesis.status: publishe