PMID- 11121532
OWN - NLM
STAT- MEDLINE
DCOM- 20010125
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 885
IP  - 1
DP  - 2000 Dec 1
TI  - Neurotrophin-3 antisense oligonucleotide attenuates nerve injury-induced 
      Abeta-fibre sprouting.
PG  - 79-86
AB  - It is proposed that following peripheral nerve injury abnormal sprouting of 
      Abeta-fibre primary afferent neurons in the spinal cord contributes to the 
      allodynia that often occurs with such injury. Allodynia is characterized as pain 
      due to a stimulus which is normally non-noxious. Our recent in vivo experiments 
      show that intrathecal administration of neurotrophin-3 (NT-3), in normal animals, 
      induces allodynia and sprouting of Abeta-fibres. In this study, we examine 
      whether intrathecal administration of NT-3 antisense oligonucleotides (50 
      microM), via an osmotic pump for 14 days, attenuates nerve injury-induced 
      sprouting and allodynia. The oligonucleotides used in this study were 
      phosphorothioate modified and control experiments, using an ELISA, confirm that 
      intrathecal administration of the antisense induces a significant decrease in 
      NT-3 levels in the spinal cord. All surgery was conducted on anaesthetized Wistar 
      rats (sodium pentobarbitone, i.p. 50 mg/kg). Consistent with previous studies, 
      transganglionic labelling of Abeta-fibres with choleragenoid-horseradish 
      peroxidase (C-HRP) shows that complete transection of the sciatic nerve induces 
      an expansion of C-HRP label into lamina II of the spinal dorsal horn. Using image 
      analysis, we find that intrathecal administration of NT-3 antisense attenuates 
      the density of C-HRP labelling in lamina II in nerve injured animals. A NT-3 
      sense oligonucleotide (50 microM) has no effect. To test the effect of NT-3 
      antisense on allodynia, the nociceptive flexion reflex is examined, using an Ugo 
      Basile Analgesymeter, in animals with partial sciatic nerve ligation. Intrathecal 
      administration of 50 microM NT-3 antisense significantly attenuates nerve 
      injury-induced allodynia, whereas the sense oligonucleotide has no effect. These 
      results provide further evidence that endogenous NT-3 contributes to both nerve 
      injury-induced Abeta-fibre sprouting and allodynia and demonstrates the potential 
      of neurotrophin-3 antisense oligonucleotides as therapeutic agents for 
      neuropathic pain.
FAU - White, D M
AU  - White DM
AD  - Department of Anaesthesia and Pain Management, University of Sydney, Royal North 
      Shore Hospital, N.S.W. 2065, St. Leonards, Australia. debbeau@ozemail.com.au
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Neurotrophin 3)
RN  - 0 (Oligonucleotides, Antisense)
RN  - EC 1.11.1.- (Horseradish Peroxidase)
SB  - IM
MH  - Animals
MH  - Horseradish Peroxidase
MH  - Injections, Spinal
MH  - Ligation
MH  - Male
MH  - Nerve Fibers, Myelinated/*physiology
MH  - Nerve Regeneration/*physiology
MH  - Neurotrophin 3/*genetics
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Posterior Horn Cells/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Sciatic Nerve/cytology/injuries/*physiology
MH  - Sciatica/physiopathology/therapy
EDAT- 2000/12/21 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/21 11:00
PHST- 2000/12/21 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/21 11:00 [entrez]
AID - S0006-8993(00)02940-1 [pii]
AID - 10.1016/s0006-8993(00)02940-1 [doi]
PST - ppublish
SO  - Brain Res. 2000 Dec 1;885(1):79-86. doi: 10.1016/s0006-8993(00)02940-1.