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 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.
Bennett
G J
GJ
Department of Neurology, MCP Hahnemann University, Philadelphia, Pennsylvania 19102-1192, USA.
D000818:Animals; D002490:Central Nervous System / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D009424:Nervous System Physiological Phenomena; D010146:Pain / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate