PMID- 19361551
OWN - NLM
STAT- MEDLINE
DCOM- 20090923
LR  - 20220408
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Print)
IS  - 0889-1591 (Linking)
VI  - 23
IP  - 6
DP  - 2009 Aug
TI  - Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor 
      activation.
PG  - 851-60
LID - 10.1016/j.bbi.2009.04.001 [doi]
AB  - There is growing recognition that psychological stress influences pain. Hormones 
      that comprise the physiological response to stress (e.g., corticosterone; CORT) 
      may interact with effectors of neuropathic pain. To test this hypothesis, mice 
      received a spared nerve injury (SNI) after exposure to 60 min restraint stress. 
      In stressed mice, allodynia was consistently increased. The mechanism(s) 
      underlying the exacerbated pain response involves CORT acting via glucocorticoid 
      receptors (GRs); RU486, a GR antagonist, prevented the stress-induced increase in 
      allodynia whereas exogenous administration of CORT to non-stressed mice 
      reproduced the allodynic response caused by stress. Since nerve injury-induced 
      microglial activation has been implicated in the onset and propagation of 
      neuropathic pain, we evaluated cellular and molecular indices of microglial 
      activation in the context of stress. Activation of dorsal horn microglia was 
      accelerated by stress; however, this effect was transient and was not associated 
      with the onset or maintenance of a pro-inflammatory phenotype. Stress-enhanced 
      allodynia was associated with increased dorsal horn extracellular 
      signal-regulated kinase phosphorylation (pERK). ERK activation could indicate a 
      stress-mediated increase in glutamatergic signaling, therefore mice were treated 
      prior to SNI and stress with memantine, an N-methyl-D-aspartate receptor (NMDAR) 
      antagonist. Memantine prevented stress-induced enhancement of allodynia after 
      SNI. These data suggest that the hormonal responses elicited by stress exacerbate 
      neuropathic pain through enhanced central sensitization. Moreover, drugs that 
      inhibit glucocorticoids (GCs) and/or NMDAR signaling could ameliorate pain 
      syndromes caused by stress.
FAU - Alexander, Jessica K
AU  - Alexander JK
AD  - Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH 
      43210, USA.
FAU - DeVries, A Courtney
AU  - DeVries AC
FAU - Kigerl, Kristina A
AU  - Kigerl KA
FAU - Dahlman, Jason M
AU  - Dahlman JM
FAU - Popovich, Phillip G
AU  - Popovich PG
LA  - eng
GR  - R01 NS037846-09/NS/NINDS NIH HHS/United States
GR  - 1R01 NR 010806/NR/NINR NIH HHS/United States
GR  - NS 37846/NS/NINDS NIH HHS/United States
GR  - R01 NS037846-10/NS/NINDS NIH HHS/United States
GR  - R01 NS037846/NS/NINDS NIH HHS/United States
GR  - R01 NR010806/NR/NINR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090408
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 320T6RNW1F (Mifepristone)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Corticosterone/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mifepristone/pharmacology
MH  - Pain/*etiology/pathology/*psychology
MH  - Pain Measurement/drug effects
MH  - Peripheral Nervous System Diseases/*complications/pathology
MH  - Phosphorylation
MH  - Posterior Horn Cells/drug effects
MH  - Receptors, Glucocorticoid/agonists/antagonists & inhibitors/*physiology
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Restraint, Physical
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stress, Psychological/*complications/*psychology
PMC - PMC2735409
MID - NIHMS135173
COIS- The authors declare no conflict of interest pertaining to the data described 
      herein.
EDAT- 2009/04/14 09:00
MHDA- 2009/09/24 06:00
PMCR- 2010/08/01
CRDT- 2009/04/14 09:00
PHST- 2009/02/07 00:00 [received]
PHST- 2009/03/31 00:00 [revised]
PHST- 2009/04/01 00:00 [accepted]
PHST- 2009/04/14 09:00 [entrez]
PHST- 2009/04/14 09:00 [pubmed]
PHST- 2009/09/24 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - S0889-1591(09)00103-2 [pii]
AID - 10.1016/j.bbi.2009.04.001 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2009 Aug;23(6):851-60. doi: 10.1016/j.bbi.2009.04.001. Epub 
      2009 Apr 8.