Update on the neurophysiology of pain transmission and modulation: Focus on the NMDA-receptor

Pain is detected by two different types of peripheral nociceptor neurons, C -fiber nociceptors with slowly conducting unmyelinated axons, and A-delta n ociceptors with thinly myelinated axons. During inflammation, nociceptors b ecome sensitized, discharge spontaneously, and produce ongoing pain. Prolon ged firing of C-fiber nociceptors causes release of glutamate which acts on N-methyl-D-aspartate (NMDA) receptors in the spinal cord. Activation of NM DA receptors causes the spinal cord neuron to become more responsive to all of its inputs, resulting in central sensitization. NMDA-receptor antagonis ts, such as dextromethorphan, can suppress central sensitization in experim ental animals. NMDA-receptor activation not only increases the cell's respo nse to pain stimuli, it also decreases neuronal sensitivity to opioid recep tor agonists. In addition to preventing central sensitization, co-administr ation of NMDA-receptor antagonists with an opioid may prevent tolerance to opioid analgesia. J Pain Symptom Mange 2000;19:S2-S6. (C) U.S. Cancer Pain Relief Committee, 2000.