title: Specific involvement in neuropathic pain of AMPA receptors and adapter proteins for the GluR2 subunit.
abstract: Chronic pain states arise from peripheral nerve injury and are inadequately treated with current analgesics. Using intrathecal drug administration in a rat model of neuropathic pain, we demonstrate that AMPA receptors play a role in the central sensitisation that is thought to underpin chronic pain. The GluR2 subunit of the AMPA receptor binds to a number of intracellular adapter proteins including GRIP, PICK1 and NSF, which may link the receptor to proteins with signalling, scaffolding and other roles. We implicate for the first time a possible role for GRIP, PICK1 and NSF in neuropathic sensitisation from experiments with cell-permeable blocking peptides mimicking their GluR2 interaction motifs and also demonstrate differential changes in expression of these proteins following peripheral nerve injury. These studies suggest a critical involvement of protein:protein complexes associated with the AMPA receptor in neuropathic pain, and the possibility that they may have potential as novel therapeutic targets.
authors.affiliation: Centre for Neuroscience Research, Division of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK.
authors.forename: Emer M
authors.initials: EM
authors.lastname: Garry
authors.forename: Andrew
authors.initials: A
authors.lastname: Moss
authors.forename: Roberta
authors.initials: R
authors.lastname: Rosie
authors.forename: Ada
authors.initials: A
authors.lastname: Delaney
authors.forename: Rory
authors.initials: R
authors.lastname: Mitchell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fleetwood-Walker
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D052066:N-Ethylmaleimide-Sensitive Proteins; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009687:Nuclear Proteins; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D033921:Vesicular Transport Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D010455:Peptides; D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse; C498737:Nsf protein, rat; C104722:glutamate receptor ionotropic, AMPA 2