Glutamate is the primary excitatory neurotransmitter of the central nervous system and is normally released by pain-signaling afferent neurons as they synapse on central pain pathways in the spinal cord. The persistent release of glutamate, due to peripheral injury or inflammation, leads to the activation of N-methyl-D-aspartate (NMDA) receptors. This process of activation has been shown to play a crucial role in mediating the phenomenon of "wind up" pain, a state in which spinal neurons become hyper-responsive to repetitive painful stimulation.