PMID- 16150544
OWN - NLM
STAT- MEDLINE
DCOM- 20060125
LR  - 20210112
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 117
IP  - 3
DP  - 2005 Oct
TI  - NMDA receptor antagonist treatment at the time of nerve injury prevents 
      injury-induced changes in spinal NR1 and NR2B subunit expression and increases 
      the sensitivity of residual pain behaviours to subsequently administered NMDA 
      receptor antagonists.
PG  - 421-432
LID - 10.1016/j.pain.2005.07.005 [doi]
AB  - Spinal NMDA receptors (NMDA R) are important in neuropathic sensitisation and 
      acute administration of antagonists can provide temporary attenuation of 
      sensitisation. If establishment of the chronic pain state could be prevented by 
      brief administration of such agents at or around the time of nerve injury 
      (pre-emptive analgesia) it might be possible to avoid many of the unacceptable 
      side effects associated with repeated administration of these or other 
      antagonists. Several reports describe aspects of effective pre-emptive analgesia 
      from NMDA R antagonists in animal models of neuropathic pain. The first aim of 
      the present study was to make a direct comparison of changes in mechanical 
      allodynia, cold allodynia and thermal hyperalgesia following nerve injury, 
      demonstrating their increasing degree of susceptibility to pre-emptive NMDA R 
      antagonist treatment. Secondly, we used immunoblotting and immunohistochemistry 
      to investigate the effects of nerve injury on NMDA receptor subunit expression, 
      revealing increased expression of NR2B, but not NR2A and reduced NR1 in the 
      superficial dorsal horn. These changes were attenuated following NMDA receptor 
      antagonist pre-treatment. Thirdly, we investigated the pharmacological properties 
      of residual mechanical allodynia and cold allodynia that remained after 
      pre-emptive treatment and revealed a greater sensitivity to NMDA R antagonists. 
      These findings indicate that in addition to a marked suppression of thermal 
      hyperalgesia and cold allodynia, pre-emptive treatment with NMDA R antagonist 
      causes a lasting change in spinal NMDA R complexes such that remaining mechanical 
      allodynia should be more effectively targeted by NMDA R antagonists.
FAU - Wilson, John A
AU  - Wilson JA
AD  - Centre for Neuroscience Research, Division of Veterinary Biomedical Sciences, The 
      Royal (Dick) School of Veterinary Studies, The University of Edinburgh, 
      Summerhall, Edinburgh EH9 1QH, UK Department of Anaesthesia, Critical Care & Pain 
      Medicine, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, UK Centre for 
      Integrative Physiology (Membrane Biology Group), School of Biomedical and 
      Clinical Laboratory Sciences, University of Edinburgh EH8 9XD, UK.
FAU - Garry, Emer M
AU  - Garry EM
FAU - Anderson, Heather A
AU  - Anderson HA
FAU - Rosie, Roberta
AU  - Rosie R
FAU - Colvin, Lesley A
AU  - Colvin LA
FAU - Mitchell, Rory
AU  - Mitchell R
FAU - Fleetwood-Walker, Susan M
AU  - Fleetwood-Walker SM
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Blotting, Western/methods
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Antagonists/*administration & dosage/therapeutic use
MH  - Functional Laterality
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Pain/complications/*prevention & control
MH  - Pain Measurement
MH  - Pain Threshold/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reaction Time/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Spinal Cord/*drug effects/metabolism/pathology
MH  - Time Factors
MH  - Trauma, Nervous System/complications/drug therapy
EDAT- 2005/09/10 09:00
MHDA- 2006/01/26 09:00
CRDT- 2005/09/10 09:00
PHST- 2005/05/02 00:00 [received]
PHST- 2005/05/02 00:00 [revised]
PHST- 2005/07/12 00:00 [accepted]
PHST- 2005/09/10 09:00 [pubmed]
PHST- 2006/01/26 09:00 [medline]
PHST- 2005/09/10 09:00 [entrez]
AID - 00006396-200510000-00020 [pii]
AID - 10.1016/j.pain.2005.07.005 [doi]
PST - ppublish
SO  - Pain. 2005 Oct;117(3):421-432. doi: 10.1016/j.pain.2005.07.005.