PAIN-CENTRAL SENSITIZATION, MECHANISMS

SUMMARY

1. High-intensity and/or prolonged nociceptor activation in association with injury and inflammation ⟹ NMDA receptor activation ⟹ central sensitisation.

2. This leads to increased intracellular Ca²⁺ ⟹ changes in gene expression and associated phenotypic shifts in dorsal horn nociceptive neurons.

3. NMDA receptor activation underlies dorsal horn wind-up and manifests as a broadening of sensory fields and allodynia associated with secondary hyperalgesia.

4. Central sensitization similarly occurs at higher CNS synapses and is similar to long-term potentiation (LTP) that underlies memory formation in hippocampal networks.

5. Such strengthened nociceptive networks may persist after healing of peripheral injury.

6. NMDA receptor antagonists (ketamine) attenuate central sensitization but their efficacy may be limited by inhibition of higher CNS synapses involved in conscious processing and memory.

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