Altered Pain Processing


  • 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
      • > in pain-relevant areas
  • Disrupted default mode network
    • •Active at rest
      •Deactivates with task
      •Chronic pain →Decreased deactivation
      •May contribute to cognitive



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