Bennett G J
Department of Neurology, MCP Hahnemann University, Philadelphia, Pennsylvania 19102-1192, USA.
J Pain Symptom Manage. 2000 Jan;19(1 Suppl):S2-6. doi: 10.1016/s0885-3924(99)00120-7.
Pain is detected by two different types of peripheral nociceptor neurons, C-fiber nociceptors with slowly conducting unmyelinated axons, and A-delta nociceptors with thinly myelinated axons. During inflammation, nociceptors become sensitized, discharge spontaneously, and produce ongoing pain. Prolonged firing of C-fiber nociceptors causes release of glutamate which acts on N-methyl-D-aspartate (NMDA) receptors in the spinal cord. Activation of NMDA receptors causes the spinal cord neuron to become more responsive to all of its inputs, resulting in central sensitization. NMDA-receptor antagonists, such as dextromethorphan, can suppress central sensitization in experimental animals. NMDA-receptor activation not only increases the cell's response to pain stimuli, it also decrease neuronal sensitivity to opioid receptor agonists. In addition to preventing central sensitization, co-administration of NMDA-receptor antagonists with an opioid may prevent tolerance to opioid analgesia.
