Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

Abstract

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.

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

“…19). Since active smooth muscle contraction is required for afferent nociceptive signaling and pseudoaffective response occurrence in response to CRD (33), the action on enteric neurons may have decreased the intensity of afferent discharge during CRD.…”

The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse

“…Abdominal pain is a hallmark symptom of IBS, and feeding rodents probiotics or altering the gut microbiome with antibiotics [16][17][18][19][20] changes pseudoaffec-tive responses evoked by colorectal distension (CRD). Active smooth muscle contraction is necessary for nociceptive afferent signaling in response to CRD 21 and we have previously demonstrated that probiotics can affect the excitability of myenteric neurons, 22 thereby altering the intensity of propagated peristaltic contractions. Taken together, the data thus suggest that the change in excitability of myenteric neurons after exposure to certain bacterial species could be modulating the nociceptive response.…”

Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

“…In daily life, strong compression of the colon wall by giant migrating contractions serves as the mechanical stimulus for evoked pain in these patients (10). The pain lasts nearly as long as balloon distension or as long as a giant migrating contraction is present anywhere in the colon (26). However, most diseases that cause peripheral nerve lesions also induce a feeling of ongoing pain/discomfort (neuropathic pain), as well as other aversive sensations, such as burning, numbness, tingling, and pricking, suggesting that peripheral nerve lesions may induce multiple types of affective feelings in addition to evoked pain (28).…”