Pathophysiology of pain

Question 1

General Somatosensory Pain Pathway

Answer 1

1. First Order Neurons (primary afferent neuron) PNS

• Nociceptor sense noxious stimulus
• cell body in dorsal root ganglion (DRG) or trigeminal ganglion to face, for ex)
• synapses in doral horn with second order neuron

2. Second Order Neurons (CNS)

• cell bodies in spinal cord
• crosses immediately in anterior white matter of cord
• ascend in spinothalamic tract to VPL nucleus of thalamus

3. Third Order Neurons (CNS)

• VPL thalamus
• project to somatosensory cortex
• via posterior limb of internal capsule
• Perception of pain

Question 2

Pain transduction

Answer 2

• Different sensory receptors respond to different types of stimuli
• exist at free nerve endings of primary afferent neurons
• Types:
  
  • Mechanical (stretch, pressure, sharp pain)
  • Chemical (histamines, prostanoids, etc)
  • Thermal (hot/cold)
  • Polymodal (can detect multiple things)
• Physical stimuli converted into electrical impulses

Question 3

Pain CONDUCTION

Answer 3

Within peripheral nerve:

• A delta fibres
  
  • light myelination
  • FAST transmitters
  • “first pain”
  • well localized pain
  • also inhibit interneurons which stop C fibres from transmitting
• C Fibres:
  
  • unmyelinated
  • activated by bradykinin, cytokines, sub P etc
  • DELAYED transmitters
  • dull, aching burning pain
  • poor localization, large receptive fields
  • significant in visceral pain

Question 4

Chemical mediators of pain

Answer 4

Substances released when tissue is damaged, which activates nociceptors:

• Arachidonic acid
• glutamate
• prostaglandins
• substance P
• bradykinins
• potassium
• noradrenaline
• 5HT
• lactic acid

Question 5

Pathophysioloyg of neurogenic inflammation

Answer 5

• neuromodulator release
  
  • substance P
  • ATP
  • glutamate
• acts on peripheral blood vessels, mast cells, sympathetic nerves
• causes vasodilation, vascular permeability, etc

Question 6

Descending modulation of pain

Answer 6

• Sensory cortex neurons project down –>
• Periaqueductal gray in midbrain
  
  • neurons project down into medulla –>
• Stimulate neurons in nucleus raphe magnus
  
  • neurons project down through spinal cord
  • inhibitory effect on second order sensory neurons in spinal cord
  • stimulate interneurons in cord –>
  • inhibitory interneurons inhibit second order sensory neuron
• Endogenous opioids are released in this pathway, release firing of action potential on second order neuron

Question 7

Endogenous opioids and receptors

Answer 7

• B-endorphins (mu receptors)
• Dynorphins (bind to kappa receptors)
• Enkephalins (bind to delta receptors)

Question 8

Central sensitization

Answer 8

• “Wind up”
• Prolonged C fibre firing leads to increased presynaptic release of neurotransmitters
• causes depolarization of post synaptic neurons
• NMDA receptor on ion channel normally blocked by magnesium ion
• prolonged firing of C fibre releases magnesium ion
• calcium flows through, increases excitability, potentiates post synaptic response

Question 9

Somatosensory system

Answer 9

• “body wall” to brain
• skin to parietal lung and peritoneum
• oral mucosa

Question 10

Visceral pain receptors

Answer 10

• Polymodal
• C fibres
  
  • Mechanosensory
  • Chemoreceptors
  • Thermoreceptors

Question 11

Visceral innervation

Answer 11

• unmyelinated C fibres
• afferent nerves
• have wide spread through spinal cord and may project to other segments
• poorly localized and referred pain
• Shares many spinal root levels, convergence of afferent nerves