Research Award for Neurogastroenterology 2022

The Neurogastroenterology Foundation 2022 Award was presented by the Chairman of the Neurogastroenterology Foundation, Prof. Dr. Thomas Frieling, during Visceral Medicine 2022 in Hamburg. This year, the prize went in equal parts (clinic/basic) to PD Dr. rer. medic. Adriane Icenhour, research associate at the Department of Medical Psychology and Medical Sociology at the Ruhr University Bochum for her work on visceral pain and the mechanisms of healthy and disturbed visceroception along the gut-brain axis and to Dr. med. med. Moritz Middelhoff, assistant and junior research group leader of the II. medical clinic at the Klinikum rechts der Isar of the TU Munich for his work on intestinal neuro-epithelial communication with a focus on epithelial stem cell modulation by neuronal messengers.

We extend our warmest congratulations and look forward to the awardees' guest contributions at the 2023 Annual Meeting in Berlin!

My work is inspired by translational research at the intersection of psychology, neuroscience and neurogastroenterology. The overarching goal of our experimental approaches is a deeper understanding of the mechanisms of visceral pain and its emotional and cognitive modulators along the gut-brain axis in humans.

My focus includes pain-related learning and memory processes, their influence on pain anticipation and pain experience, and the underlying psychoneurobiological correlates. This motivation led to the research work "When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm" (NeuroImage 2021), which was awarded the prize of the Neurogastroenterology Foundation. The experimental magnetic resonance imaging study examined learning and extinction of interoceptive stimuli-induced visceral pain-related fear in an innovative paradigm of contextual interoceptive conditioning. We were able to show for the first time that previously neutral interoceptive signals from the gastrointestinal tract can become important predictors of visceral pain through associative learning with visceral pain.

Taken together, our findings provide relevant insights into mechanisms underlying symptom-related fear, visceral hypervigilance, and maladaptive avoidance behavior as central factors in the pathophysiology of gut-brain axis disorders. They significantly expand our understanding of central nervous and centrally mediated cognitive and emotional processes in gut-brain communication with significant clinical implications in the context of neurogastroenterology.

Icenhour A, Petrakova L, Hazzan N, Theysohn N, Merz CJ, Elsenbruch S (2021). When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm. Neuroimage, 238:118229. doi: 10.1016/j.neuroimage.2021.118229. PMID: 34082119

Intestinal stem cells are essential for maintaining intestinal homeostasis and regeneration after tissue damage, but they can also be the origin of malignant tumor growth. The function of intestinal stem cells is tightly regulated by the intestinal stem cell niche, which is composed of soluble signaling molecules and neighboring cells of the mucosa. The enteric nervous system with enteric neurons and glial cells and their neurotransmitters is considered an essential part of this niche. Our work aims to understand the neuro-epithelial interaction in more detail with a focus on the modulation of intestinal stem cells through neuronal signaling. For the first time, we were able to show in detail that intestinal stem cells are subject to tight cholinergic modulation and that Tuft cells contribute to the regular function of the cholinergic niche (Middelhoff et al., 2020). In another work, which was awarded the Prize for Neurogastroenterology 2022, we were able to identify significant differences in the cellular response of enteric ganglion cells to acute intestinal tissue damage (Middelhoff et al., 2022). Based on this work, we hope to identify mechanisms that can be used to promote intestinal regeneration and prevent malignant tissue transformation.

Adult enteric Dclk1-positive glial and neuronal cells reveal distinct responses to acute intestinal injury. Middelhoff M*, Valenti G*, Tomassoni L, Ochiai Y, Belin B, Takahashi R, Malagola E, Nienhüser H, Finlayson M, Hayakawa Y, Zamechek LB, Renz BW, Westphalen CB, Quante M, Margolis KG, Sims PA, Laise P, Califano A, Rao M, Gershon MD, Wang TC. Am J Physiol Gastrointest Liver Physiol. 2022 Jun 1;322(6):G583-G597. doi: 10.1152/ajpgi.00244.2021. PMID: 35319286; * contributed equally