Astrocytic ERK/STAT1 Signaling Contributes to Maintenance of Stress-Related Visceral Hypersensitivity in Rats

The rostral anterior cingulate cortex (rACC) has been found to be an important brain region in mediating visceral hypersensitivity. However, the underlying mechanisms remain unclear. This study aimed to explore the role of astrocytes in the maintenance of visceral hyper-sensitivity induced by chronic water avoidance stress (WAS) as well as the potential signaling pathway that activates astrocytes in the rACC. We found that ACC-reactive astrogliosis resulted in the overexpression of c-fos, TSP-1, and BDNF in stress-related visceral hypersensitivity rats. Visceral hypersensitivity was reversed by pharmacological inhibition of astrocytic activation after WAS, as were the overexpression of c-fos, TSP-1 and BDNF. Activation of the astrocytic Gi-path-way increased the visceral sensitivity and expression of c-fos, TSP-1, and BDNF. Visceral hyper-sensitivity was also ameliorated by the pharmacological inhibition of ERK and STAT1 phosphorylation after WAS. Furthermore, inhibition of the ERK-STAT1 cascade reduced astrocytic activation. These findings suggest that astrocytic ERK/STAT1 signaling in the rACC contributes to the maintenance of stress-related visceral hypersensitivity.Perspective: Visceral hypersensitivity is a key factor in the pathophysiology of irritable bowel syn-drome. This study highlights the important role of astrocytic ERK/STAT1 signaling in activating astro-cytes in the rostral anterior cingulate cortex, which contributes to visceral hypersensitivity.(c) 2022 by United States Association for the Study of Pain, Inc.

Automated summary

The rostral anterior cingulate cortex (rACC) and astrocytes play crucial roles in mediating visceral hypersensitivity induced by stress. The activation of astrocytes through the ERK/STAT1 signaling pathway contributes to the maintenance of stress-related visceral hypersensitivity.