PMID- 17917111
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20220321
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 35
IP  - 3
DP  - 2007 Jun
TI  - Pain facilitation and activity-dependent plasticity in pain modulatory circuitry: 
      role of BDNF-TrkB signaling and NMDA receptors.
PG  - 224-35
AB  - Pain modulatory circuitry in the brainstem exhibits considerable synaptic 
      plasticity. The increased peripheral neuronal barrage after injury activates 
      spinal projection neurons that then activate multiple chemical mediators 
      including glutamatergic neurons at the brainstem level, leading to an increased 
      synaptic strength and facilitatory output. It is not surprising that a 
      well-established regulator of synaptic plasticity, brain-derived neurotrophic 
      factor (BDNF), contributes to the mechanisms of descending pain facilitation. 
      After tissue injury, BDNF and TrkB signaling in the brainstem circuitry is 
      rapidly activated. Through the intracellular signaling cascade that involves 
      phospholipase C, inositol trisphosphate, protein kinase C, and nonreceptor 
      protein tyrosine kinases; N-methyl-D-aspartate (NMDA) receptors are 
      phosphorylated, descending facilitatory drive is initiated, and behavioral 
      hyperalgesia follows. The synaptic plasticity observed in the pain pathways 
      shares much similarity with more extensively studied forms of synaptic plasticity 
      such as long-term potentiation (LTP) and long-term depression (LTD), which 
      typically express NMDA receptor dependency and regulation by trophic factors. 
      However, LTP and LTD are experimental phenomena whose relationship to functional 
      states of learning and memory has been difficult to prove. Although mechanisms of 
      synaptic plasticity in pain pathways have typically not been related to LTP and 
      LTD, pain pathways have an advantage as a model system for synaptic modifications 
      as there are many well-established models of persistent pain with clear measures 
      of the behavioral phenotype. Further studies will elucidate cellular and 
      molecular mechanisms of pain sensitization and further our understanding of 
      principles of central nervous system plasticity and responsiveness to 
      environmental challenge.
FAU - Ren, Ke
AU  - Ren K
AD  - Department of Biomedical Sciences, Dental School & Program in Neuroscience, 
      University of Maryland, 650 W. Baltimore St., Baltimore, MD 21201-1586, USA. 
      kren@umaryland.edu
FAU - Dubner, Ronald
AU  - Dubner R
LA  - eng
GR  - R01 DE015374/DE/NIDCR NIH HHS/United States
GR  - NS059028/NS/NINDS NIH HHS/United States
GR  - DE11964/DE/NIDCR NIH HHS/United States
GR  - DA10275/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Hyperalgesia/metabolism
MH  - Inflammation/metabolism
MH  - Neuronal Plasticity/*physiology
MH  - Pain/*metabolism/physiopathology
MH  - Receptor, trkB/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Signal Transduction/*physiology
RF  - 117
EDAT- 2007/10/06 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/10/06 09:00
PHST- 2006/08/01 00:00 [received]
PHST- 1999/11/30 00:00 [revised]
PHST- 2007/01/08 00:00 [accepted]
PHST- 2007/10/06 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/10/06 09:00 [entrez]
AID - MN:35:3:224 [pii]
AID - 10.1007/s12035-007-0028-8 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2007 Jun;35(3):224-35. doi: 10.1007/s12035-007-0028-8.