Altered Pain Processing

CENTRAL SENSITIZATION

• Lots of parallel processes
• Neuroplastic changes alter the functional
  connectivity of the CNS
• Increased nociceptive signaling
• Innocuous input now causes pain

Altered Pain Processing: Periphery
• Damage → release of chemical mediators → increased sensitivity of primary afferents
• Immune response àincreased sensitivity of primary afferents
• Local vasodilation and extravasation  →Secondary Hyperalgesia
• Dependent upon ongoing peripheral injury

Altered Pain Processing: Spinal Cord

• Many pro-nociceptive compounds in dorsal horn
• Brain-derived Neurotrophic Factor (BDNF)
  Released by primary afferents
  Enhance response of dorsal horn neurons
• Prostaglandins
  ↑neurotransmitter release
  Spontaneous depolarization of dorsal horn neurons
• Independent of ongoing peripheral injury
• Wind up
  •Repeated C fiber stimulation→ enhanced dorsal horn
  neuron excitability
  •Process similar to long-term potentiation
  •↑ density and expression of receptors
  •↑transcription and expression of receptors and
  prostaglandins/COX2 enzymes
  •Later phase – transcriptional changes
  •Personal factors may predispose
• Role of the Interneuron
  • Largely inhibitory function
  • Decreased inhibitory input to 2nd order neuron
  • • Cell death
    • Decreased synaptic strength
    • Imbalance of excitatory and inhibitory activity
• Aβ fiber changes
  • Synapse onto nociceptor-specific 2nd order neurons
  • Release of Substance P (pro-nociceptive)

 

Altered Pain Processing: Immune System

• Glial Cells
  • CNS: Microglia, astrocytes
  • PNS: Satellite cells
• Function
  • Feed neurons
  • Maintain homeostasis
  • “Insulate” pain circuit
• Response to nerve injury:
  • Numerous, complex glia-neuronal interactions
  • Proliferation, hypertrophy, glial “reaction”
  • Disrupted homeostatic mechanismà neuron hyper
  excitability, CNS edema
  • The release of multiple pro-inflammatory/pro-nociceptive

Altered Pain Processing: Brain

• Increased activation of pain neuromatrix
• Involvement of additional cortical areas
• Cortical reorganization
• Altered neurochemistry
  • •Decreased opioid receptors
    •Decreased NAA concentration
    •Marker of neuronal integrity
    •Contralateral thalamus, DLPFC
    •Correlates with pain intensity
• Brain structural changes
  • •Decreased grey matter
    •Global
    • > in pain-relevant areas
• Disrupted default mode network
  • •Active at rest
    •Deactivates with task
    •Chronic pain →Decreased deactivation
    •May contribute to cognitive
    changes

 

SOURCE: http://www.ppta.org/docs/default-source/default-document-library/pain-sed-yp-2018-final.pdf?sfvrsn=0