What is the contribution of the NMDA receptor to the production of pain?
Glutamate that is released from primary afferent fibers acts upon two major receptor types in the dorsal horn: the AMPA and the NMDA receptors. Under normal conditions, the NMDA receptor is blocked by the presence of a magnesium ion in the channel. When neurons are depolarized via glutamate action at the AMPA receptor, the magnesium block is relieved, and glutamate action at the NMDA receptor is effective. This results in entry of calcium into the postsynaptic neuron, which in turn activates a variety of second messenger systems that produce long-term biochemical and molecular changes in these neurons.
The physiological consequence of these changes is a hyperexcitability of the dorsal horn neuron (i.e., central sensitization). This is manifest as an increase in the size of the receptive field of nociresponsive neurons, a decreased threshold, and a potential for spontaneous activity of the neuron. The allodynia (pain produced by nonnoxious stimuli) and hyperalgesia (exacerbated pain produced by noxious stimuli) associated with nerve injury may reflect NMDA-mediated long-term changes in dorsal horn neuronal processing.