Cellular neuroplasticity mechanisms mediating pain persistence.
Transmission of noxious-stimulus-evoked inputs in the spinal and trigeminal systems is mediated primarily through excitatory glutamatergic synapses using alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Glutamatergic synapses exhibit multiple forms of short-lasting and long-lasting synaptic plasticity. Persistent enhancement of nociceptive transmission, known as "central sensitization," is a form of lasting plasticity that is similar mechanistically to long-term potentiation of glutamatergic transmission in other regions of the central nervous system. This potentiation of AMPA/kainate transmission is dependent upon the activity of NMDA receptors, which become enhanced following noxious peripheral stimulation as a result of several convergent mechanisms. Central sensitization is thus an expression of increased synaptic gain at glutamatergic synapses in central nociceptive-transmission neurons and thereby contributes importantly to pain hypersensitivity. In addition, recent evidence has revealed a new player in the mechanisms underlying pain hypersensitivity following nerve injury--microglia. Understanding of the roles of microglia may lead to new strategies for the diagnosis and management of neuropathic pain.
Salter
Michael W
MW
The University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada. mike.salter@utoronto.ca
D019706:Excitatory Postsynaptic Potentials; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D017628:Microglia / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009433:Neural Inhibition; D009473:Neuronal Plasticity / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D009435:Synaptic Transmission; D014278:Trigeminal Nuclei / Q000502:physiology
D017470:Receptors, Glutamate; D020928:Mitogen-Activated Protein Kinases