PMID- 14622147
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 18
IP  - 9
DP  - 2003 Nov
TI  - BDNF sensitizes the response of lamina II neurons to high threshold primary 
      afferent inputs.
PG  - 2467-76
AB  - Brain-derived neurotrophic factor (BDNF) is up-regulated and released in the 
      dorsal horn following peripheral inflammation and has therefore been implicated 
      in spinal mechanisms of sensitization. Despite these observations, the mechanisms 
      associated with such a role for BDNF are not yet fully determined. Here, we 
      investigate the effect of BDNF on dorsal root-evoked synaptic transmission in 
      lamina II neurons. In a transverse spinal cord slice preparation from neonatal 
      rats (P1-15), the whole cell patch-clamp technique was used to record from these 
      neurons. Brief application of BDNF (50-200 ng/mL) facilitated the evoked synaptic 
      currents; they remained enhanced even after BDNF was washed out. A significant 
      minority of cells was minimally affected by BDNF and consistent with this, not 
      all neurons in lamina II were immunoreactive for the tyrosine kinase (trk) B 
      receptor. No facilitation was elicited when N-methyl-d-aspartate (NMDA) receptors 
      were blocked with D-APV, when the postsynaptic NMDA receptors were selectively 
      blocked with intracellular MK-801, or when postsynaptic neurons were loaded with 
      BAPTA. Additionally, inhibiting phospholipase C (PLC) or protein kinase C (PKC) 
      prior to BDNF application completely blocked facilitation. However, once synaptic 
      current underwent BDNF-induced facilitation, the PKC inhibitors failed to reverse 
      the effect, suggesting that PKC is needed for initiation, but not maintenance of 
      BDNF-induced facilitation. These results demonstrate that BDNF functions at the 
      spinal level to enhance synaptic efficacy in an NMDA receptor-dependent manner 
      and requires the action of the PLC/PKC pathway. This action of BDNF may 
      contribute to central sensitization and exaggerated pain states.
FAU - Garraway, Sandra M
AU  - Garraway SM
AD  - Department of Neurobiology and Behaviour, State University of New York, Stony 
      Brook NY 11794-5230, USA.
FAU - Petruska, Jeffrey C
AU  - Petruska JC
FAU - Mendell, Lorne M
AU  - Mendell LM
LA  - eng
GR  - 2 RO1 NS 16996/NS/NINDS NIH HHS/United States
GR  - 5PO1 NS 39420/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chelating Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Afferent Pathways/drug effects/physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Chelating Agents/pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Egtazic Acid/*analogs & derivatives/pharmacology
MH  - Electric Stimulation
MH  - Electrophysiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Ganglia, Spinal/*physiology
MH  - Immunohistochemistry
MH  - Neurons/chemistry/*drug effects/*physiology
MH  - Patch-Clamp Techniques
MH  - Protein Kinase C/antagonists & inhibitors/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/analysis
MH  - Receptors, N-Methyl-D-Aspartate/physiology
MH  - Spinal Cord/*drug effects/*physiology/physiopathology
MH  - Synaptic Transmission/*drug effects
MH  - Type C Phospholipases/antagonists & inhibitors/physiology
EDAT- 2003/11/19 05:00
MHDA- 2004/01/17 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - 2982 [pii]
AID - 10.1046/j.1460-9568.2003.02982.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2003 Nov;18(9):2467-76. doi: 10.1046/j.1460-9568.2003.02982.x.