D2 | Abstract 02

Annual NUTRIM Symposium 18 November 2020


From nociception to pain: the nucleus of the solitary tract serves a key role in visceral nociception in humans

A.B. Beckers1, L. van Oudenhove2, Z.Z.R.M. Weerts1, N. Priovoulos3, H.I. Jacobs3,4,5, B.A. Poser4, D. Ivanov4, A.A.M. Masclee1, D. Keszthelyi1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands;
2Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
3Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, Netherlands;
4Faculty of Psychology and Neuroscience, Department of Cognitive Neuroscience, Maastricht University, Maastricht, Netherlands;
5Gordon Center for Medical Imaging, Department of Radiology, Massachusetts, General Hospital/Harvard Medical School, Boston, United States.

Brain imaging studies in patients with disorders of the brain-gut interaction, such as irritable bowel syndrome, have demonstrated increased responsiveness of cortical regions implicated in pain modulation. However, experimental designs have been limited to non-physiological stimuli (e.g. rectal balloon distension). Moreover, previously used imaging techniques have not allowed for detailed visualization of the brainstem, which is suspected to have an important relay function in pain signaling. We aimed to explore the role of the brainstem in visceral pain using a nutrient-derived chemo-nociceptive stimulus.

Eighteen healthy female volunteers were included. A nasoduodenal tube was inserted during two separate test days. Capsaicin, the pungent principle of chili peppers, was used as a chemo-nociceptive stimulus to elicit a mild visceral pain response. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin and placebo (saline solution). During infusion, functional magnetic resonance imaging (fMRI) data and concomitant abdominal pain ratings were acquired. Ultrahigh-field strength fMRI (7T) was used to enable acquisition of high-resolution images of the brainstem.

Significantly increased brain activation during capsaicin infusion, as compared to placebo, was observed in brain regions implicated in pain processing, including the subgenual anterior cingulate cortex, anterior midcingulate cortex, insula, ventral thalamus and nucleus of the solitary tract. Brain responses in the ventral thalamus, pregenual anterior cingulate cortex and anterior insula were more pronounced in subjects who reported abdominal pain (visual analogue scale > 10mm), as compared to subjects who experienced no pain. On the contrary, responses at the level of the nucleus of the solitary tract were independent of subjective pain ratings.

The nucleus of the solitary tract has a key role in visceral nociception. It remains to be established which factors contribute to the differences in perceptive responses. These factors may include the involvement of non-vagal and descending inhibitory mechanisms.

NUTRIM | School of Nutrition and Translational Research in Metabolism
NUTRIM aims to contribute to health maintenance and personalised medicine by unraveling lifestyle and disease-induced derangements in metabolism and by developing targeted nutritional, exercise and drug interventions. This is facilitated by a state of the art research infrastructure and close interaction between scientists, clinicians, master and PhD students.