Background:
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.

Methods:
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.

Results:
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.

Conclusions:
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.