Effects of nematode infection on sensitivity to intestinal distension: role of tachykinin NK2 receptors.
Distension of the rat intestine causes a depressor response which is predictive of nociception. This study investigated the effects of previous infection with Nippostrongylus (N.) brasiliensis on the sensitivity to intestinal distension and the role of tachykinin NK2 receptors. The tachykinin NK2 receptor antagonist, SR48968 (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloropheny l)butyl]benzamide) inhibited the nociceptive response (ED50 = 0.7 mg/kg) in control rats. In post-N. brasiliensis-infected rats sensitivity to intestinal distension was increased which was accompanied by an increase in the apparent potency value of SR48968 (ED50 = 0.1 mg/kg). The hypersensitivity was limited to areas of hypermastocytosis. It is concluded that the post-inflammatory changes that occur in post-infected rats increase visceral sensitivity and the apparent potency of tachykinin NK2 receptor antagonists.
McLean
P G
PG
Department of Pharmacology-Toxicology, INRA, Toulouse, France.
Picard
C
C
Garcia-Villar
R
R
Moré
J
J
Fioramonti
J
J
Buéno
L
L
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003106:Colon / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003108:Colonic Diseases / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D004108:Dilatation, Pathologic; D007411:Intestinal Diseases, Parasitic / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D007579:Jejunal Diseases / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D007583:Jejunum / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D009559:Nippostrongylus; D010147:Pain Measurement; D009195:Peroxidase / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017206:Strongylida Infections / Q000503:physiopathology*
D001549:Benzamides; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C073839:SR 48968; D009195:Peroxidase