Specific involvement in neuropathic pain of AMPA receptors and adapter proteins for the GluR2 subunit

Emer M Garry, Andrew Moss, Roberta Rosie, Ada Delaney, Rory Mitchell, Susan M Fleetwood-Walker

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)10-22
Number of pages13
JournalMolecular and Cellular Neuroscience
Issue number1
Publication statusPublished - Sept 2003

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Carrier Proteins
  • Cell Membrane
  • Chronic Disease
  • Excitatory Amino Acid Antagonists
  • Functional Laterality
  • Glutamic Acid
  • Hyperalgesia
  • Male
  • N-Ethylmaleimide-Sensitive Proteins
  • Neuralgia
  • Nuclear Proteins
  • Pain Threshold
  • Peptides
  • Peripheral Nervous System Diseases
  • Protein Binding
  • Protein Subunits
  • Protein Transport
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, AMPA
  • Recombinant Fusion Proteins
  • Reflex
  • Synaptic Transmission
  • Vesicular Transport Proteins
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid


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