C fibers cause central sensitization of the dorsal horn in the spinal cord in response to their hyperactivity. The mechanism underlying this phenomenon involves the release of glutamate by these pathologically sensitized C fibers. The glutamate interacts with the postsynaptic NMDA receptors, which aids the sensitization of the dorsal horn. Presynaptic neuronal voltage-gated N-calcium channels are largely responsible for the release of this glutamate as well as the neuropeptide, substance P. The expression of presynaptic neuronal voltage-gated N-calcium channels increases after a nerve lesion or repeated stimulation. NMDA receptor activation (by glutamate) enhances postsynaptic Nitric Oxide Synthase. Nitric Oxide is thought to migrate back to the presynaptic membrane to enhance the expression of the voltage-gated N-calcium channels resulting in a pain wind-up phenomenon. This abnormal central sensitization cycle results in increased pain (hyperalgesia) and pain responses from previously non-noxious stimuli evoke a pain response (allodynia).