Wind-up pain is caused by activation of normally dormant NMDA receptors.Activated NMDA receptors cause - influx of Calcium into Dorsal Horn Wide Dynamic Range interneurons resulting in a cycle of - increased production/sensitization/number of NMDA receptors & increased release of Glutamate/Substance-P at presynaptic sites This positive feedback loop results in a marked increase in the pain signal ultimately perceived by the brain.
Blocking NMDA receptors to limit neurotoxicity January 24th Structural biologists at Cold Spring Harbor Laboratory (CSHL) and collaborators at Emory University have obtained important scientific results likely to advance efforts to develop new drugs targeting NMDA receptors in the brain. - See more at: http://allblackclothes.com/index.php?cID=159#sthash.WRAN7awJ.dpuf
NMDA (N-methyl-D-aspartate) is the selective agonist that binds to NMDA receptors but not to other glutamate receptors. The NMDA receptor (NMDAR) is the predominant molecular device for controlling synaptic plasticity and memory function. The NMDAR is a type of ionotropic glutamate receptor. Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not stimulate the receptors as strongly). In addition, NMDARs also require the binding of the co-agonist glycine.
A new pharmaceutical technology licensed in February by the Corporate Ventures office at The Hospital for Sick Children (SickKids) may help treat neuropathic and inflammatory pain in children and adults, but without the serious side effects that can accompany currently available treatments.
My friend, Duncan Momaney coauthored this published paper at age 22!!! I bow humbly before a man who works hard to advance knowledge! - The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats