Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain.
We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective 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 nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M(1) and M(2). The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK(1), NK(2), and NK(3); serotonin receptors 5-HT(1A), 5-HT(2)/5-HT(1C), 5-HT(3), and 5-HT(4); and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.
Sarna
Sushil K
SK
Division of Gastroenterology, Dept of Internal Medicine, The Univ of Texas Medical Branch at Galveston, Galveston, TX 77555-1064, USA. sksarna@utmb.edu
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D003085:Colic / Q000503:physiopathology; D004285:Dogs; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D058919:Purinergic P2 Receptor Antagonists; D018039:Receptors, Tachykinin; D012702:Serotonin Antagonists; D016210:Methacholine Chloride; D001285:Atropine; D014700:Verapamil; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester