Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans

Abraham B. Beckers*, Lukas van Oudenhove, Zsa Zsa R. M. Weerts, Heidi I. L. Jacobs, Nikos Priovoulos, Benedikt A. Poser, Dimo Ivanov, Ali Gholamrezaei, Qasim Aziz, Sigrid Elsenbruch, Ad A. M. Masclee, Daniel Keszthelyi

*Corresponding author for this work

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ABSTRACT: Neuroimaging studies have revealed important pathomechanisms related to disorders of brain-gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multi-echo multiband 7T functional magnetic resonance imaging (fMRI) and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin (the pungent principal in red peppers) and placebo (saline). During infusion, fMRI data and concomitant symptom ratings were acquired. Of 26 healthy female volunteers included, 18 were included in the final analysis. Significantly increased brain activation over time during capsaicin infusion, as compared to placebo, was observed in brain regions implicated in pain processing, in particular the NTS. Brain activation in the thalamus, cingulate cortex and 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, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.

Original languageEnglish
Pages (from-to)1520-1529
Number of pages10
Issue number8
Early online date15 Nov 2021
Publication statusPublished - Aug 2022


  • Brain imaging
  • Nucleus of the solitary tract
  • Visceral pain
  • Gut-brain axis
  • FMRI
  • BOLD
  • EPI

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