Effects of tachykinin receptor antagonists on the rat jejunal distension pain response

Abstract

Distension of the rat intestine causes a cardiovascular response which is indicative of nociception. Since tachykinins are involved in nociception, we tested the effect of neurokinin receptor antagonists against the distension-induced response. The jejunal distension-induced depressor responses were inhibited in a dose-dependent fashion by CP 99,994 (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine, tachykinin NK1 receptor antagonist, ED50 = 0.8 mg/kg) and SR 48968 (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloropheny l)butyl]benzamide, tachykinin NK2 receptor antagonist, ED50 = 0.7 mg/kg). SR 142801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N-methylacetamide, tachykinin NK3 receptor antagonist, 0.3-10 mg/kg) did not significantly affect the depressor responses to jejunal distension. In addition, CP 99,994 (3 mg/kg) and SR 48968 (3 and 10 mg/kg) reduced sensitivity to distension as revealed by a 2.7-fold (CP 99.994, 3 mg/kg), 2.6-fold (SR 48968, 3 mg/kg) and 4.7-fold (SR 48968, 10 mg/kg) increase in the threshold pressure. Intestinal compliance was not affected by the antagonists. In conclusion, these results suggest that tachykinin NK1 and NK2 but not NK3 receptors are possibly involved in the rat jejunal distension pain response.