RIIBS · Role of membrane potential Instabilities in Irritable Bowel Dysease
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-10-01 → 2025-09-30
- EU contribution
- €175,920
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
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Results in brief
Role of membrane potential Instabilities in Irritable Bowel Dysease
Chronic visceral pain, such as that experienced by people with Irritable Bowel Syndrome (IBS), represents one of the most prevalent yet least understood forms of long-term pain. Despite affecting millions of Europeans and generating substantial healthcare and socioeconomic burden, the biological mechanisms that initiate and maintain visceral pain are still unclear. Current treatments often provide limited relief, and the lack of mechanistic understanding slows the development of new, effective therapies. This project set out to uncover how sensory neurons—the cells that detect signals from the body—become abnormally excitable in IBS. A particular focus was placed on a recently discovered phenomenon called membrane potential instabilities (MPIs). These small, spontaneous voltage fluctuations may help explain why some neurons fire excessively, contributing to chronic pain. Understanding when and why these instabilities appear, and how they are altered in IBS, could reveal new therapeutic targets and improve how visceral pain is managed. The project pursued three integrated objectives: 1. Determine how IBS-like conditions modify electrical activity in mouse sensory neurons, with special attention to MPIs. 2. Develop a new optical technique that allows fast, high-resolution measurements of neuronal electrical activity, enabling the study of MPIs at subcellular levels. 3. Evaluate whether similar mechanisms occur in human sensory neurons, supporting the translation of findings into human biology. Together, these objectives aim to generate fundamental knowledge that can guide the development of new analgesic strategies, reduce the burden of chronic visceral pain, and support European leadership in neuroscience research and innovation.
Data: CORDIS, © European Union
Project objective
Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders with a prevalence of 4-10% worldwide, characterized by recurrent abdominal pain. Pain is tightly related with noxious stimulus detection carried out by peripheral sensory neurons (PSNs). However, how those neurons generate ongoing activity, encoding constant or slow stimuli is still uncertain, and the current textbook model for sensory transduction and encoding fails to explain it. During the last years, many authors have proposed membrane potential instabilities (MPIs), a voltage dependent phenomenon that consists in subthreshold membrane potential fluctuations, as the mechanism underlying ongoing activity and demonstrated its upregulation in pathologies coursing with neuropathic and bone cancer pain, both in animal models and patients. Nevertheless, the role of MPIs in visceral pain remains completely unexplored. In this project we aim to characterize the role of MPIs and excitability changes in the development of IBS pain, as well as its underlying mechanisms. Furthermore, we will develop a new model to study the subcellular distribution of MPIs and action potential encoding in this pathology, using voltage optical recordings. Finally, to assure the translatability of our results, we will study sensory neurons from IBS patients and the possibility to treat them through MPIs pharmacological disruption, opening new treatment approaches. In the long-term, RIIBS action will lead to increased insight in sensory information encoding, the pathophysiology of IBS and ultimately to improved clinical management of visceral pain. This is the adequate moment to carry this action, as the host institution counts with top-notch facilities to make it feasible, the host supervisors have recently generated a novel animal model reproducing IBS and have access to clinical patients, and voltage optical recordings have been living an exponential refinement in the last years.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
- View on CORDIS
- DOI: 10.3030/101105721
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e511bfb93a&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5215be7a0&appId=PPGMS
Data: CORDIS, © European Union