ACTIVATION OF THE ARYL HYDROCARBON RECEPTOR REDUCES VISCERAL HYPERSENSITIVITY IN A MOUSE MODEL OF COLITIS IN REMISSION

The aryl hydrocarbon receptor (AhR) is a protein found on specific pain-sensing neurons in the gut. However, its role in regulating abdominal pain has not been fully understood. Studies have shown that around half of individuals with inflammatory bowel disease (IBD) experience ongoing abdominal pain, even when their condition is in remission.

Previous research has found reduced production of indole derivatives, which are microbial byproducts, in IBD patients. Indoles are known to interact with AhR. The researchers proposed that the lack of AhR activation might contribute to increased pain sensitivity in these individuals. They used mice that had recently experienced colitis to investigate the role of AhR in this context.

By activating AhR using natural and synthetic compounds, they found that both male and female mice experienced reduced sensitivity to abdominal pain. In contrast, blocking AhR function using medications stopped the protective effects of indoles. The researchers discovered that AhR activation by a certain compound increased the expression of a specific potassium channel in the pain-sensing neurons.

This decrease in neuronal activity significantly reduced pain signals in the spinal cord. Genetic analysis revealed that the types of indole-producing bacteria in the gut differed between male and female mice, with specific bacteria being more abundant in male mice. These findings suggest that supplementing with specific indoles in mice that had colitis can help alleviate their ongoing abdominal pain.

This suggests that targeting AhR could potentially be a new treatment strategy for managing abdominal pain in IBD patients who are in remission.