Salutary Effects of Tachykinin Receptor Antagonists in a Rat Model of Postoperative Ileus1

BackgroundPostoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK1–3 antagonists, SR140333, SR48968, and SR142801, was investigated.Materials and methodsIntestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats.ResultsDiethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals—UN: 61.17 ± 5.47, 62.10 ± 8.30, and 56.70 ± 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 ± 2.07 and 9.70 ± 1.15 cm, respectively. SR140333 (3–30 μg/kg), SR48968 (1–30 μg/kg), and SR142801 (3–10 μg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 ± 1.08, 21.70 ± 0.19, and 25.0 ± 1.34 cm. The combinations of submaximal doses of NK1 and NK3, NK2 and NK3 and NK1, and NK2 and NK3 antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK1 + NK2 antagonists) acted additively, the intestinal transit reaching 26.60 ± 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP.ConclusionsSR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK1 and NK2 antagonists being most beneficial.