Role of brain CRF signaling pathways in development of postoperative gastric ileus in rats

Abdominal surgery (AS) delays gastric emptying (GE) through CRF receptors (CRF-R). CRF-R1 contributes to central CRF-induced sympathetic activation. CRF1 knockout mice did not develop gastric ileus.

Aims: To characterize the CRF-R type involved in postoperative gastric ileus and the role of central sympathetic activation.

Methods: Anestetized adult fasted male SD rats underwent midline celiotomy and 60s cecum palpation or anesthesia alone. CRF2 antagonsist, astressin2-B (Ass2B), was injected iv just before and the CRF1 antagonist, CP-154,526 (CP) was injected sc at 60min and icv at 30min prior to celiotomy. GE of a methylcellulose solution given intragastrically was measured 100min after the end of the surgery. In other studies, brains were processed for c-Fos and double labeling with CRF and tyrosine hydroxylase (TH) by immunohistochemistry.

Results are presented as mean±SEM *=P<0.05. Results: AS inhibits GE (22±4.5%) compared to controls (53±6.4%*). CP (5,10 or 20mg/kg, sc) dose-dependently prevented AS-induced delayed GE (12.7±8.4%, 33.3±10%* and 46.9±4.0%* resp). Ass2B (200ìg/kg, iv) did not influence AS (GE: 16.0±5.0% vs. 21.3±6.6%) but blocked the selective CRF2 agonist, human urocortin II (20 ìg/kg, iv)-induced delayed GE (57.8±11.3% vs. 16.5±12.2%*). CP (icv, 1mg/rat) partly prevented AS effect (32.5¹ 8.1% vs. icv vehicle+AS: 12.3±2.8%*). The CRF antagonists did not influence basal GE. AS-induced Fos expression in TH neurons of the ventrolateral medulla and CRF neurons of the hypothalamic paraventricular nucleus was reduced by CP.

Conclusion: Brain CRF1 signaling pathways activating sympathetic outflow is part of the mechanisms leading to gastric postoperative ileus.