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Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier
Yulin Huang1, Chenchen Wang1, Xinyu Tian1
1Department of Anaesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, 210008, Jiangsu province, China.
Inflammation
|January 29, 2020
Summary
Pioglitazone, a PPARγ agonist, alleviates chronic pain in colitis by repairing the intestinal barrier and upregulating tight junction proteins. This PPARγ-tight junction signaling pathway offers a potential therapeutic target for colitis-associated pain.
Area of Science:
- Gastroenterology and Immunology
- Neuroscience and Pain Research
Background:
- Colitis impairs intestinal mucosal integrity and is associated with chronic pain.
- Peroxisome proliferator-activated receptor-γ (PPARγ) is an anti-inflammatory factor in the gut, but its role in colitis-associated pain is unclear.
Purpose of the Study:
- To investigate the therapeutic role of pioglitazone, a PPARγ agonist, in relieving colitis-associated hyperalgesia.
- To elucidate the mechanism involving PPARγ and tight junction proteins in DSS-induced colitis pain.
Main Methods:
- Dextran sodium sulfate (DSS)-induced colitis model in C57BL/6 mice.
- Assessment of intestinal barrier function, hyperalgesia, and molecular changes using immunofluorescence, H&E staining, and Western blot.
- Evaluation of pioglitazone's effects on pain thresholds, inflammatory markers, and neuronal signaling.
Main Results:
- Pioglitazone treatment ameliorated DSS-induced colitis and associated mechanical hyperalgesia.
- Pioglitazone upregulated tight junction proteins ZO-1 and Claudin-5, restoring intestinal barrier integrity.
- Pioglitazone reduced colon inflammation, inhibited spinal cord neuroinflammation, and decreased pain signaling.
Conclusions:
- Pioglitazone effectively treats colitis-associated hyperalgesia by enhancing intestinal barrier function via PPARγ-mediated upregulation of tight junction proteins.
- The PPARγ-tight junction protein pathway represents a promising therapeutic target for managing chronic pain in colitis.
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