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Neural Control of GI Motility (& Drug Correlations)

Neural Control of GI Motility
Overview
Intrinsic control
  • The Enteric Nervous System (ENS):
    • Is intrinsic to the GI wall.
    • Runs the length of the GI tract.
    • Primarily coordinates local activity in the digestive tract via two key nerve plexuses:
1. The submucosal plexus (aka Meissner's plexus) 2. The myenteric plexus (aka Auerbach's plexus)
Extrinsic control
  • Parasympathetic innervation stimulates digestion: it stimulates GI motility and the secretion of hormones and digestive juices.
    • Remember its tagline is "Rest and Digest".
  • Sympathetic nervous system inhibits digestive activity.
    • Remember its tagline is "fight or flight" – neither of which have anything to do with digestion.
Intrinsic System
Anatomy of the digestive tract.
From inside to outside:
  • The GI lumen
  • The mucosal layer
    • Epithelial layer
    • Lamina propria
    • Muscularis mucosae
  • The submucosal layer
    • The submucosal plexus (Meissner's plexus) lies within the outer portion of this layer.
  • The smooth muscle (muscularis externa) layer.
    • The inner, circular layer.
    • The myenteric plexus (Auerbach's plexus) lies in between the inner, circular and outer, longitudinal layers.
    • The outer, longitudinal layer.
The different orientations of the inner, circular and outer, longitudinal muscle layers allow us to distinguish them.
  • The adventitia/serosa layer; it's serosa within the abdominal cavity.
Extrinsic system
Parasympathetic nervous system
  • Cranial nerve 10 (the vagus nerve) innervates the gut.
    • It innervates the upper 2/3 of the GI tract (ie, the foregut and midgut).
    • It is this wandering nature of the vagus nerve all the way to the gut that give it its name "vagus," which is Latin for "wandering."
  • Spinal neurons S2 to S4 of the intermediolateral cell column of the sacral spinal cord innervate pelvic splanchnic nerves, which innervate the gut.
    • They innervate the lower 1/3 of the GI tract (ie, the hindgut).
Sympathetic nervous system
  • Originates from the T5 to L2 neurons of the intermediolateral cell column.
  • Abdominopelvic splanchnic nerves innervate prevertebral ganglia, which innervate the GI tract.
Interaction of the extrinsic and intrinsic systems
Extrinsic neuronal input innervates the myenteric plexus
  • The extrinsic neuronal inputs converge on a neuron in the myenteric plexus.
  • This innervates a neighboring neuron, which extends into the submucosa to innervate a neuron of the submucosal plexus,
which then innervates the muscular layer of the mucosa to activate or inhibit GI motility.
Pharmacological correlations
Neurotransmitters
  • Acetylcholine INcreases GI motility (it's the major parasympathetic neurotransmitter – the "D" in the "SLUDS" acronym stands for defecation or diarrhea.
  • Norepinephrine DEcreases GI motility (it's the major postganglionic sympathetic neurotransmitter).
  • Opioid peptides DEcrease GI motility.
  • Serotonin INcreases GI motility – serotonin syndrome causes diarrhea.
Drugs
  • Amitriptyline decreases circulating acetylcholine, so it decreases GI motility.
  • Donepezil increases circulating acetylcholine, so it increases GI motility.
  • Beta-blockers decrease circulating norepinephrine, so they increase GI motility.
  • Venlafaxine increases circulating norepinephrine, so it decreases GI motility.
  • Morphine is an opioid agonist, so it decreases GI motility.
  • Naltrexone is an opioid antagonist, so it increases GI motility.
  • Quetiapine decreases circulating serotonin, so it decreases GI motility.
  • Citalopram increases circulating serotonin, so it increases GI motility.