Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow-transit

S K King1, J R Sutcliffe, S-Y Ong

  • 1Department of General Surgery, Royal Children's Hospital, Melbourne, Australia.

Insights

Pediatric slow-transit constipation (STC) may involve reduced nerve fibers. Specifically, children with STC showed lower substance P (SP) and vasoactive intestinal peptide (VIP) nerve density in the proximal colon compared to controls.

Area of Science:

  • Gastroenterology
  • Pediatric Surgery
  • Colorectal Surgery

Background:

  • Slow-transit constipation (STC) is a recognized pediatric condition with an unknown etiology.
  • Abnormalities in neurotransmitters like substance P (SP), vasoactive intestinal peptide (VIP), and nitric oxide (NO) are suspected contributors to STC.
  • Nerve fiber density in the colon's circular muscle layer is a key area of investigation.

Purpose of the Study:

  • To examine the density of nerve fibers containing SP, VIP, and NO in the colonic circular muscle of children with STC.
  • To compare these findings with pediatric controls (normal colonic transit and anorectal retention) and adult samples.
  • To investigate potential age-related and regional variations in these nerve fibers.

Main Methods:

  • Colonic biopsies from the transverse and sigmoid colon were obtained from adults and children.
  • Fluorescence immunohistochemistry was used to detect nerve fibers containing NO synthase (NOS), VIP, and SP.
  • Confocal microscopy quantified the percentage area of nerve fibers for each transmitter in the circular muscle.

Main Results:

  • Nerve fiber density followed the order NOS > VIP > SP in the colon's circular muscle.
  • Pediatric samples exhibited higher nerve fiber density than adult samples.
  • Children with STC had significantly lower SP and VIP nerve fiber density in the proximal colon compared to children with normal transit.

Conclusions:

  • Age-related decreases in colon circular muscle nerve fiber density were observed.
  • SP nerve fiber density showed regional variation, being higher in the distal colon.
  • A subset of pediatric STC patients (approximately 1/3) presented with reduced SP or VIP nerve fiber density in the proximal colon, suggesting a potential etiological link.
Abstract

Related Concept Videos

Drugs for Treatment of Constipation-Predominant IBS01:21

Drugs for Treatment of Constipation-Predominant IBS

Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
Drugs Affecting GI Tract Motility: Other Laxatives01:20

Drugs Affecting GI Tract Motility: Other Laxatives

Laxatives are primarily used to alleviate constipation, a common gastrointestinal disorder characterized by infrequent bowel movements and difficulty passing stools. They work by various mechanisms to increase the volume or frequency of bowel movements. The primary modes of action of laxatives include increasing stool bulk, softening the stool, stimulating intestinal motility, and osmotically drawing water into the intestines.
Osmotic or saline laxatives, like magnesium hydroxide or milk of...
Drugs Affecting GI Tract Motility: Bulk-Forming and Stimulant Laxatives01:22

Drugs Affecting GI Tract Motility: Bulk-Forming and Stimulant Laxatives

Laxatives enhance bowel movements and alleviate constipation. They augment the stool's bulk, stimulate intestinal muscle contractions, draw water into the intestines, or soften the stool. There are five key types of laxatives: bulk laxatives, stimulant laxatives, osmotic laxatives, stool softeners, and lubricant laxatives.
Bulk-forming laxatives, such as psyllium, methylcellulose, and polycarbophil, absorb water in the intestine, increasing stool bulk and promoting bowel movement. This makes...
Diverticular Disease of the Colon01:27

Diverticular Disease of the Colon

Diverticular disease involves the formation of diverticula—small sac-like outpouchings of the colonic wall—and their complications. It most commonly affects the sigmoid colon due to higher intraluminal pressure and structural vulnerability. It results from structural weakness and increased pressure in the colon, producing pseudodiverticula that may remain silent or progress to inflammation and serious complications.Structure of DiverticulaIn diverticulosis, these outpouchings are...
Drugs Affecting GI Tract Motility: Adsorbents as Antidiarrheal Agents01:20

Drugs Affecting GI Tract Motility: Adsorbents as Antidiarrheal Agents

Diarrhea is characterized by the occurrence of frequent, watery bowel movements. Various factors can trigger diarrhea, including viral or bacterial infections, foodborne illnesses, side effects from certain medications, and underlying digestive disorders. If not adequately managed, diarrhea can lead to complications such as dehydration, electrolyte imbalances, and nutrient deficiencies. Severe diarrhea can lead to significant weight loss, malnutrition, and weakened immune function.
Adsorbents...