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- W3151567405 abstract "Background: Patients with irritable bowel syndrome (IBS) suffer from abdominal pain and associated constipation, diarrhea, and bloating. Some IBS patients (~35%) have visceral hypersensitivity to noxious experimental stimuli (e.g., colonic distension). We previously reported that colonic NMDA receptor signaling in IBS patients may be an underlying mechanism leading to visceral hypersensitivity that is reversed with Dextromethorphan (J Pain 2012;13:901-9). The current study was performed to determine if down regulation of in vivo NMDA receptor signaling via upregulation of miR-23a using miRNA mimics reverses visceral hypersensitivity in an IBS animal model. Methods: Male rats (n=12) received onehour water avoidance (WA) stress per day, for 10 consecutive days to induce visceral hypersensitivity as measured by colonic distension using a barostat. Intrathecal injection of miR-23a mimics (n=6 rats) or miRNA control (n=6 rats) was then performed and visceral hypersensitivity was measured 7 days later following injections. Following colonic barostat testing, all rats were sacrificed to measure colonic NMDA receptors and miR-23a expression using fluorescence in situ hybridization (FISH) using tyramide signal amplification (TSA) technology. Results: Rats treated with intrathecal injection of miR-23a mimics had decreased visceral hypersensitivity compared to rats that received intrathecal control miRNA (p<0.01). There was a significant increase in colonic miR-23a expression and a decrease in NMDA receptor signaling in rats that received miR-23a mimcs that correlated with decreased visceral hypersensitivity.Conclusion:Down regulation of NMDA receptor signaling through augmentation of miR-23a reverses visceral hypersensitivity in WA rats. Aberrant expression of key miRNAs dysregulate downstream targets such as NMDA receptors which contribute to visceral hypersensitivity in IBS patients. This data suggests that miR-23a could be a new therapeutic target for attenuating visceral hypersensitivity in IBS patients. Work supported by NIH grant (R01DK099052)." @default.
- W3151567405 created "2021-04-13" @default.
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- W3151567405 date "2015-01-01" @default.
- W3151567405 modified "2023-09-23" @default.
- W3151567405 title "Mo2036 Genome-Wide Transcriptional Profiling Demonstrates Differences Between Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD) and Heathy Controls" @default.
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