Spinal mediators of hyperalgesia.
Neuronal plasticity associated with altered sensations arising from tissue damage involves both established (e.g. substance P and excitatory amino acids) and novel (e.g. nitric oxide and metabolites of arachidonic acid) mediators released from terminals of primary afferent neurons or synthesised in the spinal cord. These and other mediators lead to activity-dependent synaptic plasticity and enhanced sensitivity to noxious stimuli (hyperalgesia). Activation of the N-methyl-D-aspartate (NMDA) receptor results in a calcium-dependent production of nitric oxide, while activation of alpha-amino-3-hydroxy-5-methylisoxazole-5-propionate (AMPA)-and 1,3- trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD)-sensitive glutamate receptors results in a phospholipase A2 (PLA2)-mediated production of different intracellular mediators, including arachidonic acid. Thermal hyperalgesia requires NMDA receptor activation and is primarily mediated by production of nitric oxide. Mechanical hyperalgesia requires AMPA and metabotropic glutamate receptor coactivation, and is primarily mediated by cyclo-oxygenase products of arachidonic acid metabolism.
Meller
S T
ST
Department of Pharmacology, University of Iowa College of Medicine, Iowa City.
Gebhart
G F
GF
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D018846:Excitatory Amino Acids; D009498:Neurotoxins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016718:Arachidonic Acid; D009569:Nitric Oxide; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001120:Arginine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester