PMID- 12435470
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20190818
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 100
IP  - 1-2
DP  - 2002 Nov
TI  - Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal 
      mice while antisense directed against either BDNF or trkB, prevent 
      inflammation-induced hyperalgesia.
PG  - 171-81
AB  - Although known primarily for its role in neuronal development, brain-derived 
      neurotrophic factor (BDNF) has also recently been implicated in processes 
      mediated by the adult nervous system, such as spinal nociception. Peripheral 
      inflammation increases expression of BDNF preferentially in dorsal root ganglion 
      cells that contain substance P and/or calcitonin gene-related peptide, known 
      nociceptive transmitters for which synthesis is also increased during 
      inflammatory states. Expression of the tyrosine kinase receptor that selectively 
      binds BDNF, trkB, is increased in the spinal dorsal horn during inflammation as 
      well. Additionally, intrathecal (i.t.) administration of the BDNF-scavenging 
      protein trkB-IgG attenuates inflammation-induced behavioral responses. 
      Collectively, this evidence implicates BDNF in spinal nociceptive processes. Here 
      we show that, in normal mice, i.t. BDNF produces an acute, dose-dependent thermal 
      hyperalgesic response. Selective inhibition of BDNF expression by i.t. antisense 
      oligodeoxynucleotide treatment produces antinociception in normal mice and 
      attenuates carrageenan-induced hyperalgesia. Further, we demonstrate that i.t. 
      antisense treatment directed against the full-length trkB receptor (trkB.FL) 
      attenuates carrageenan-induced hyperalgesia. Consistent with a trkB.FL-mediated 
      mechanism, the i.t. administration of another trkB ligand, neurotrophin-4/5, also 
      produces hyperalgesia while the trkC agonist neurotrophin-3, which weakly 
      cross-reacts with trkB, has little effect. Finally, with the accumulating 
      evidence linking BDNF to synaptic plasticity, we investigated whether 
      BDNF-induced hyperalgesia in normal mice involves the N-methyl-D-aspartate (NMDA) 
      receptor. Interestingly, i.t. co-administration of the NMDA receptor antagonist 
      D(-)-2-amino-5-phosphonovaleric acid (D-APV) with BDNF dose-dependently inhibits 
      BDNF-induced hyperalgesia, suggesting that BDNF induces acute hyperalgesic 
      responses and affects central sensitization in a process dependent on NMDA 
      receptor activation.
FAU - Groth, Rachel
AU  - Groth R
AD  - Department of Biology, Macalester College, 1600 Grand Ave, Saint Paul, MN 55105, 
      USA.
FAU - Aanonsen, Lin
AU  - Aanonsen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 9000-07-1 (Carrageenan)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism/*pharmacology
MH  - Carrageenan
MH  - Hot Temperature
MH  - Hyperalgesia/*drug therapy/immunology/*physiopathology
MH  - Inflammation/chemically induced/immunology/physiopathology
MH  - Injections, Spinal
MH  - Mice
MH  - Neuronal Plasticity
MH  - Nociceptors/drug effects/immunology
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Rats
MH  - Receptor, trkB/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Spinal Cord/immunology/physiopathology
EDAT- 2002/11/19 04:00
MHDA- 2003/03/13 04:00
CRDT- 2002/11/19 04:00
PHST- 2002/11/19 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2002/11/19 04:00 [entrez]
AID - S0304395902002646 [pii]
AID - 10.1016/s0304-3959(02)00264-6 [doi]
PST - ppublish
SO  - Pain. 2002 Nov;100(1-2):171-81. doi: 10.1016/s0304-3959(02)00264-6.