Glasgow 2005

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Glasgow 2005
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MotilityThe Brain-Gut AxisDavid G
Thompson(GI science Hope hospital)
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Website

• WWW.hop.man.ac.uk/Gastroweb/presentations

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Brain
Spinal


Vagus
ENS
Cord
Gut
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Control of GI tract function

• The Big Brain (in the head)
• The little brain (in the gut)
• the enteric nervous system ENS

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The enteric nervous system
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Programmes of the ENS(myenteric plexus)

• Peristaltic reflex
• Migrating motor complex (MMC)

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The peristaltic reflex
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The Migrating Motor ComplexMMC
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Clinical diseases of the ENS

• Oesophagus Achalasia
• Oesophageal spasm
• Stomach Gastroparesis
• Intestine Pseudo-obstruction
• Colon Slow transit constipation

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The oesophagus
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Oesophageal peristalsis
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Peristaltic reflexOesophagus
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Oesophageal clearance
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Clinical disorders of oesophageal motility

• Achalasia
• Diffuse oesophageal spasm

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Achalasia Clinical presentation

• Difficulty swallowing
• Food sticks on way down
• Solids worse than liquids

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AchalasiaPathophysiology

• Damage to the myenteric plexus of the oesophagus
• Failure of
• peristalsis of the oesophagus
• relaxation of the lower oesophageal sphincter

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Early Achalasia
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Severe Achalasia
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Achalasia (Barium swallow)
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Diffuse oesophageal spasmClinical presentation

• Anginalike chest pain
• Exacerbated by eating but not by exercise
• Pain on swallowing

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Diffuse oesophageal spasmpathophysiology

• ENS dysfunction
• Failure of inhibitory reflexes

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Diffuse oesophageal spasm
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Motility diffuse spasm
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The small intestine

• The MMC
• The Peristaltic Reflex

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The Migrating Motor ComplexMMC
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MMC progression 1
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MMC progression 2
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MMC after extrinsic denervation
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The peristaltic reflex
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Intestinal peristaltic reflexnormal motility
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Disordered intestinal motility

• Chronic intestinal pseudo-obstruction

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Intestinal pseudo-obstructionpathophysiology

• Degeneration of the ENS
• Failure of peristalsis
• Pain
• Intestinal distension
• (mimics true intestinal obstruction)

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Intestinal Peristaltic reflex intestinal
pseudo-obstruction
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Brain
Spinal


Vagus
ENS
Cord
Gut
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Vagal Spinal pathways
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Spinal pathways

• Activated by
• Distention
• Inflammation
• Ischaemia

• Result in
• Motility inhibition (ileus)
• Pain

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Vagal pathways

• Nutrient recognition
• Switch from fasting to feeding motility
• Induction of secretion
• Gastric relaxation

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The human Brain-Gut Axis

• Spinal pathways and Pain
• Spinal afferents Central Sensitisation
• Effects of attention emotion
• Vagal pathways and Response to food
• Enteroendocrine cells the vagus

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William Beaumont 1785-1853
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Beaumont with Alexis St Martin 1822
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Beaumonts observations

• Injury to mucosa causes non-painful stimuli to
  become painful
• Hypersensitivity

• Mental state increases perception of gut stimulus
• Hypervigilance

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Clinical relevance of Beaumont(Functional Gut
disorders)

• Irritable Bowel Syndrome /Non cardiac chest
  pain/Functional dyspepsia
• Aetiology unknown
• Management unsatisfactory

Normally nonpainful stimuli reported as painful
by patients
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Where is the Problem in functional gut disorders ?
Hypersensitive Gut ?
?
?
Hypervigilant CNS?
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Gut Hypersensitivity
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Injury and pain hypersensitivity
Peripheral sensitisation
Hyperalgesia at site of injury ( Peripheral
nerve) Evidence of injury at site of sensitivity
Centras
Central sensitisation
Hyperalgesia distant from site of injury
(Dorsal horn neurone) No evidence of injury at
site of sensitivity
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Normal sensory pathways
Pain
Pain
Pain
Touch

Glutamate
Spinal Cord
Spinal Cord


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Development of Central Sensitisation
Pain
Pain
Pain
Pain

Glutamate
NMDA
Spinal Cord
Spinal Cord


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Oesophageal sensitivity
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Central sensitisation and NMDA Receptor
NMDA receptors widely distributed within dorsal
horn of spinal cord NMDA receptor antagonism
in animal models Blocks central
sensitisation Clinically available NMDA
antagonist Ketamine
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Central sensitisation of the Upper Oesophagus
following acid in the Lower Oesophagus effect
of NMDA antagonism (Ketamine)
95 CI
Acid
Ketamine
Change in Pain threshold (mA)
Placebo
-30 0
30 60
90 120
N 13
p0.001
Time (mins)
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Hypervigilance and gut sensation
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Methods for measuringbrain responses to gut
stimulation

• Positron emission tomography (PET)
• Functional MRI (fMRI)

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PET images of gut stimulation
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In Functional gut disorders
Anxiety/Depression are more common
So
Could psychological factors contribute to
increased pain reporting ?
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Altering psychological state

• Alteration of emotional state
• Anticipation of pain

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Induction of altered emotional state
Neutral face
Fearful face
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Effect of altered emotional state
Neutral face and Oesophageal stimulation
Fearful face and oesophageal stimulation
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Effect of anticipation of pain
Anticipation of painful stimulation of oesophagus
Anticipation of non-painful stimulation of
oesophagus
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Where is the Problem in functional GI disorders ?
Hypersensitive Gut ?
?
?
Hypervigilant CNS?
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Brain
Spinal


Vagus
ENS
Cord
Gut
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The vagus nerve

• 90 fibres in the vagus are afferent nerves
• Fasting motility is converted to a fed pattern by
  food
• Vagotomy prevents the switch to fed pattern

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So
How does the vagus know what is in the gut ?
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Gut enteroendocrine cells
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Brain gut Peptides
Orexin
Leptin -
Vagus
Ghrelin
CCK-
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CCK Leptin
Orexin Ghrelin
Eating behaviour
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Orexin Ghrelin
CCK Leptin
Fasted
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CCK Leptin
Orexin Ghrelin
Fed
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Enteroendocrine cells and disease

• Inflammation of the gut
• Intestinal immunity(Coeliac disease)
• Intestinal infection ( Giardiasis)

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Brain
Spinal


Vagus
ENS
Cord
Gut
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Brain to Gut Pathways

• Vital for
• Swallowing
• Anorectal function

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The brainand swallowing function
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1 cm
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Pharyngeal emg response to cortical stimulation
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Surface map of amplitudes
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Asymmetry of Swallowing representation
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Asymmetry of swallowing (PET)
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Magstim vs PET Asymmetry
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Gut problems after brain injury

• Difficulty swallowing (dysphagia)

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Stroke patients dysphagic
non-dysphagic
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Stroke Recovery
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Dysphagia development
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The brainand Anorectal function
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Anal catheter
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Cortical representation of anus
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Cortical asymmetry of anus
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Brain
Spinal


Vagus
ENS
Cord
Gut
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Website

• WWW.hop.man.ac.uk/Gastroweb/presentations