Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats

AIM: To investigate the key factors in developing the trinitrobenzene sulfonic acid (TNBS)-induced post-inflammatory irritable bowel syndrome (PI-IBS) model in rats. METHODS: TNBS was administered to rats at the following conditions: (1) with different doses (20, 10, 5 mg/0.8 mL per rat); (2) with same dose in different concentrations (20 mg/rat, 25, 50 mg/mL); (3) in different ethanol percentage (25%, 50%); and (4) at depth either 4 cm or 8 cm from anus. At 5 d and 4 wk after TNBS administration, inflammation severity and inflammation resolution were evaluated. At 4 and 8 wk after TNBS application, visceral hyperalgesia and enterochromaffin (EC) cell hyperplasia were assayed by abdominal withdrawal reflex test, silver staining and capillary electrophoresis. RESULTS: Our results showed that: (1) TNBS induced dose-dependent acute inflammation and inflammation resolution. At 5 d post TNBS, the pathological score and myeloperoxidase (MPO) activity in all TNBS treated rats were significantly elevated compared to that of the control (9.48 +/- 1.86, 8.18 +/- 0.67, 5.78 +/- 0.77 vs 0, and 3.55 +/- 1.11, 1.80 +/- 0.82, 0.97 +/- 0.08 unit/mg vs 0.14 +/- 0.01 unit/mg, P < 0.05). At 4 wk post TNBS, the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control (1.52 +/- 0.38 and 0.80 +/- 0.35 vs 0, P < 0.05); (2) Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia. At 4 wk post TNBS, abdominal withdrawal reflex (AWR) threshold pressure in all TNBS-treated groups were decreased compared to that of the control (21.52 +/- 1.73 and 27.10 +/- 1.94 mmHg vs 34.44 +/- 1.89 mmHg, P < 0.05). At 8 wk post TNBS, AWR threshold pressure in 8 cm administration group was still significantly decreased (23.33 +/- 1.33 mmHg vs 36.79 +/- 2.29 mmHg, P < 0.05); (3) Ethanol percentage affected the TNBS-induced inflammation severity and visceral. hyperalgesia. In TNBS-25% ethanol-treated group, the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50% ethanol-treated group, while AWR threshold pressure were significantly elevated (36.33 +/- 0.61 mmHg vs 23.33 +/- 1.33 mmHg, P < 0.05); and (4) TNBS (5 mg/0.8 mL per rat, in 50% ethanol, 8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration. CONCLUSION: TNBS dosage, concentration, intracoIonic administration position, and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats. (C) 2012 Baishideng. All rights reserved.