Pathway

• the 3-neuron ascending chain

Mechanism for Chronic Pain

• Neuroinflammation at nociceptor (damaged organ)

  • Tissue damage → inflammatory cytokine

• Peripheral sensitization at nociceptor (nociceptive neurons)

  • Increase responsiveness and lower threshold for the nociceptive neurons

    

  • Clinically manifest as Allodynia and Hyperalgesia

• Central sensitization at CNS

  

  

  Both involving second-order neurons

  • The presence of cutaneous Allodynia is a marker of central sensitization. There is also evidence that acute medications (e.g., triptans) become less effective