We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudo-affective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of NO synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X, P2Y, and muscarinic receptors M1 and M2. The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of NO synthase. It was unaffected by the inhibition of tachykinin receptors NK1, NK2, Nk3, serotonin receptors 5-HT_1A, 5-HT₂/5-HT_1C, 5-HT₃, 5-HT₄ and muscarinic receptors. Our findings show that GMCs, but not RPCs, can initiate pseudo-affective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.