PMID- 11425916
OWN - NLM
STAT- MEDLINE
DCOM- 20010726
LR  - 20220310
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 13
DP  - 2001 Jul 1
TI  - Brain-derived neurotrophic factor increases in the uninjured dorsal root ganglion 
      neurons in selective spinal nerve ligation model.
PG  - 4891-900
AB  - Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two 
      major members of the neurotrophin family. Using immunohistochemistry and in situ 
      hybridization histochemistry, we examined the effect of L5 spinal nerve ligation 
      (SPNL), a neuropathic pain model, on the expression of BDNF in the uninjured L4 
      dorsal root ganglion (DRG). After L5 SPNL, both immunoreactivity for BDNF and the 
      hybridization intensity for BDNF mRNA increased mainly in the small- and 
      medium-sized neurons. The percentage of BDNF mRNA-expressing neurons increased in 
      the ipsilateral L4 DRG compared with the contralateral DRG from the third to 28th 
      day after ligation. A significantly greater number of BDNF-immunoreactive neurons 
      were observed in the ipsilateral L4 DRG than contralateral side 14 d after 
      ligation. To test the contribution of BDNF to the thermal hyperalgesia produced 
      in this model, we intrathecally injected anti-BDNF antibody at third day after 
      ligation. This treatment clearly attenuated thermal hyperalgesia for a few hours. 
      Almost all BDNF mRNA-expressing neurons coexpressed trkA, a high-affinity NGF 
      receptor, mRNA. The percentage of BDNF mRNA-expressing cells of trkA cells 
      significantly increased in the ipsilateral L4 DRG 14 d after ligation. 
      Furthermore, we examined the contribution of NGF on this phenotypic change using 
      ELISA, Northern blot analysis, and anti-NGF antibody. NGF content in the 
      ipsilateral L4 DRG linearly increased and reached a statistical significant level 
      14 d after L5 SPNL. Moreover, at this time point, the increase in NGF mRNA was 
      observed in the ipsilateral L5 DRG and sciatic nerve, but not in the ipsilateral 
      L4 DRG or L4 spinal nerve. Local application of anti-NGF antibody to the L4 
      spinal nerve beside the L5 spinal nerve-ligation site prevented the development 
      of thermal hyperalgesia for 5 d after ligation. Our data suggest that BDNF, which 
      increased in the uninjured L4 DRG neurons, acts as a sensory neuromodulator in 
      the dorsal horn and contributes to thermal hyperalgesia in this neuropathic pain 
      model. The contribution of locally synthesized NGF to thermal hyperalgesia was 
      also demonstrated. These dynamic alterations in the expression and content of 
      BDNF and NGF in the uninjured DRG neurons might be involved in the 
      pathomechanisms of neuropathic pain.
FAU - Fukuoka, T
AU  - Fukuoka T
AD  - Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 
      Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. tfukuoka@hyo-med.ac.jp
FAU - Kondo, E
AU  - Kondo E
FAU - Dai, Y
AU  - Dai Y
FAU - Hashimoto, N
AU  - Hashimoto N
FAU - Noguchi, K
AU  - Noguchi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Animals
MH  - Antibodies/administration & dosage
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Ganglia, Spinal/*metabolism/pathology
MH  - Hindlimb/physiopathology
MH  - Hyperalgesia/drug therapy/etiology
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Injections, Spinal
MH  - Ligation
MH  - Lumbosacral Region
MH  - Male
MH  - Mononeuropathies/complications/*physiopathology
MH  - Nerve Growth Factor/antagonists & inhibitors/genetics/metabolism
MH  - Neurons/*metabolism
MH  - Pain Measurement
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkA/genetics/metabolism
MH  - Spinal Nerves/*physiopathology
PMC - PMC6762362
EDAT- 2001/06/27 10:00
MHDA- 2001/07/28 10:01
PMCR- 2002/01/01
CRDT- 2001/06/27 10:00
PHST- 2001/06/27 10:00 [pubmed]
PHST- 2001/07/28 10:01 [medline]
PHST- 2001/06/27 10:00 [entrez]
PHST- 2002/01/01 00:00 [pmc-release]
AID - 21/13/4891 [pii]
AID - 5365 [pii]
AID - 10.1523/JNEUROSCI.21-13-04891.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Jul 1;21(13):4891-900. doi: 10.1523/JNEUROSCI.21-13-04891.2001.