Experimental colitis-induced visceral hypersensitivity is attenuated by GABA-treatment in mice

Am J Physiol Gastrointest Liver Physiol. 2024 Jan 9. doi: 10.1152/ajpgi.00012.2023. Online ahead of print.ABSTRACTUlcerative colitis (UC) is linked with inflammation of the large intestine due to an overactive response of the colon-immune system. UC is associated with weight loss, rectal bleeding, diarrhea, and abdominal pain. Given that GABA suppresses immune cell activity and the excitability of colonic afferents, and that there is a decrease in colonic GABA during UC, we hypothesized that UC-pain is due to a decrease in the inhibition of colonic afferents. Thus, restoring GABA in the colon will attenuate inflammatory hypersensitivity. We tested this hypothesis in a mouse model of colitis. Colon inflammation was induced with seven days of dextran sodium sulfate (DSS, 3%) in the drinking water. GABA (40 mg/Kg) was administered orally for the same period as DSS, and body weight, colon length, colon permeability, clinical progression of colitis (DAI), and colon histological score (HS) were assessed to determine the effects of GABA on colitis. A day after the end of GABA treatment, visceral sensitivity was assessed with balloon distention- (of the colon) evoked visceromotor response, and colon samples were collected for the measurement of GABA and cytokines. Treatment with GABA reduced the DSS-induced increase in the colon permeability, DAI, HS, and decrease in body weight and colon length. Furthermore, GABA inhibited the DSS-induced increase in the pro-inflammatory cytokines T...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research