Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat.
Tachykinins are known to be involved in the processing of information leading to central sensitization and nociception. Using an animal model of repetitive colorectal distensions (CRD), we investigated the effect of spinal administration of tachykinin receptor antagonists in the mediation of visceral hypersensitivity. Intrathecal administration of the NK(1) receptor antagonist RP-67,580 (6.5 nmol) and the NK(3) receptor antagonist R-820 (6.5 nmol) completely blocked the CRD-induced hyperalgesia for both noxious and innocuous stimuli. The intrathecal administration of SR-48,968, a tachykinin NK(2) receptor antagonist, did not affect the visceral pain threshold of hypersensitive animals. Thus, the results from the present experiment support the concept that tachykinins with actions at spinal NK(1) and NK(3) but not NK(2) receptor sites are involved in visceral hypersensitivity mediated by nociceptive and non-nociceptive afferent inputs.
Neurobiology and Digestive Motility Laboratory, CHUM Research Centre, University of Montreal, Montreal, Québec, Canada.
Geneviève-Anne
GA
Gaudreau
Victor
V
Plourde
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004064:Digestive System / Q000294:innervation* / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017833:Visceral Afferents / Q000378:metabolism*
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides; D010880:Piperidines; C109443:R 820; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C073839:SR 48968