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Neuro-immune mechanisms of visceral and respiratory hypersensitivity
Airway hyperreactivity and irritable bowel syndrome are common diseases characterized by mucosal irritation and visceral pain, leading to reduced quality of life and a substantial economic burden. Current therapies are however limited, mainly due to a lack of understanding how sensory neurons become hypersensitive to airborne contaminants, food components, cold and chemical factors produced by the microbiota lining the airways and gut mucosa. Previously, we showed that the nasal and intestinal sensory innervation hyperreact to specific chemical agonists of the polymodal nociceptors TRPV1 and TRPA1, in validated animal models and in patients with non-allergic rhinitis and irritable bowel syndrome. In this project we will further evaluate the mechanisms underlying hyperreactivity and test the hypothesis that sensory neuron hypersensitivity arises from aberrant regulation of molecular determinants of cellular excitability. We will identify novel mediators and receptors modulating pain signaling and aim to unravel the underlying molecular mechanisms of nociceptor sensitization. For this we will use state-of-the-art methods such as single cell RNA sequencing, metabolomics, microfluidic neuronal cultures and ex vivo recordings of intracellular Ca2+ and mucosal potentials in animal tissues. The final outcome of this project will enhance our understanding of the underlying pathophysiology of neural hypersensitivity and ultimately lead to a better clinical management of our patients.
Date:1 Oct 2018 → Today
Keywords:visceral hypersensitivity, airway hyperreactivity, TRP channels, mast cells, irritable bowel syndrome, non-allergic rhinitis
Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Gastro-enterology and hepatology, Endocrinology and metabolic diseases