In central sensitization, NMDA receptor–mediated plasticity leads to which of the following clinical phenomena?

• A. Hyperalgesia and allodynia
• B. Hypoalgesia
• C. Analgesia
• D. Motor neuron fatigue

Answer: (A)

In central sensitization, changes inside the spinal cord amplify pain signaling because NMDA receptor–mediated plasticity makes dorsal horn neurons more responsive. When a peripheral injury sends repeated input, NMDA receptors in these neurons become activated (the Mg2+ block is relieved by depolarization), allowing calcium to enter and trigger cascades that strengthen synapses and even alter gene expression. This heightened excitability lowers the threshold for activation and can expand the receptive fields, so stimuli that are normally non-painful become painful and painful stimuli feel more intense. Clinically, this shows up as hyperalgesia (increased pain from a noxious stimulus) and allodynia (pain from non-painful stimuli).

Other options don’t fit this mechanism. Hypoalgesia would be a reduction in pain sensitivity, not the heightened responsiveness produced by NMDA-driven plasticity. Analgesia refers to pain relief, which is the opposite of what central sensitization accomplishes. Motor neuron fatigue is unrelated to this nociceptive CNS plasticity.

So, NMDA receptor–mediated plasticity in central sensitization best explains the presence of both hyperalgesia and allodynia.