What is central sensitization and how does it alter pain perception?

• A. Decreased excitability of CNS neurons due to brief nociceptive input
• B. Heightened excitability of CNS neurons due to sustained nociceptive input with NMDA receptor–mediated plasticity, causing hyperalgesia and allodynia
• C. Increased peripheral receptor sensitivity with no CNS plasticity
• D. Activation of descending analgesic pathways leading to reduced pain

Answer: (B)

Central sensitization is the heightened responsiveness of central pain pathways to nociceptive input. When nociceptive signals stay strong or persist, neurons in the spinal cord and brain become more excitable. A key mechanism involves NMDA receptors on dorsal horn neurons; sustained input leads to calcium influx through these receptors, triggering intracellular signaling that strengthens synapses and changes gene expression. This NMDA receptor–mediated plasticity increases the efficiency of pain signaling, often with more AMPA receptors at the synapse, making neurons fire more easily.

The result is hyperalgesia—pain amplified to normally painful stimuli—and allodynia—pain evoked by stimuli that wouldn’t normally hurt. Central sensitization can also broaden receptive fields and sustain pain beyond tissue healing. Glial activation and inflammatory mediators in the CNS can further amplify this process, sometimes producing wind‑up with repeated firing of C fibers.

This concept contrasts with peripheral sensitization, which is about increased sensitivity of nociceptors outside the CNS, and with descending analgesic pathways, which suppress pain.