Stress & the microbiota–gut–brain axis in visceral pain

Abstract

Visceral pain is a global term used to describe pain originat- ing from the internal organs of the body, which affects up to 25% of the population and is a common feature of functional gastroin- testinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience co-morbid behavioral disorders, such as anxiety or depression, thus IBS is described as a biopsychosocial disorder of the gut-brain axis. Cur- rently, treatment strategies are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. The pathophysiology of visceral pain strongly implicates a role of stress in the development and exacer- bation of symptoms. In this presentation, I will discuss our recent studies in a vari- ety of rodent models of visceral pain, in particular early-life stress models as well as genetic susceptibility models. I will describe our data, demonstratinghowstress can modify central pain circuitry at the level of the spinal cord, highlighting a key role of glutamater- gic signaling. Furthermore, I will discuss the potential of employing epigenetic modifiers, specifically histone deacetylase inhibitors, as a treatment strategy for visceral pain. More recently, the role of the gut microbiota in the bi-directional communication along the gut-brain axis have been appreciated. I will present data to further support a novel role of the gut microbiota in the regulation of vis- ceral pain processes. Taken together, these findings will enhance our knowledge of the pathophysiology of visceral pain.