Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model.
METHODS
In vitro and in vivo study of a rat inflammatory pain model using nuclear factor-kappa B decoy.


OBJECTIVE
To investigate transduction efficiency of nuclear factor-kappa B decoy into dorsal root ganglion, both in vivo and in vitro, and to assess the suppression of inflammatory pain by nuclear factor-kappa B decoy.


BACKGROUND
Transcription factor nuclear factor-kappa B is reported to play a crucial role in regulating pro-inflammatory cytokine gene expression. We hypothesized that inhibiting nuclear factor-kappa B gene expression with nuclear factor-kappa B decoy may suppress inflammatory pain.


METHODS
Nuclear factor-kappa B decoy-fluorescein isothiocyanate (FITC) was induced in explant culture, endoneurally injected into the sciatic nerve, and its transduction efficiency into dorsal root ganglion measured. For behavioral testing, 12 rats received plantar injections of complete Freund's adjuvant and were divided into 3 groups: decoy group, single endoneural injection of 10 microL of nuclear factor-kappa B decoy (n = 4); saline group, single endoneural injection of 10 microL of saline (n = 4); and naïve group, untreated (n = 4). Behavioral testing was performed using von Frey filaments and a Hargreaves device with a heat source.


RESULTS
Total transduction efficiency of nuclear factor-kappa B decoy-FITC was 53.6% in vitro and 20.5% in vivo. No statistical differences were observed with respect to types of cell size distributions of all FITC-positive neurons. In behavioral testing, withdrawal latencies or thresholds significantly differed between the decoy group and the saline group from 2 to 14 days after surgery in the mechanical allodynia experiments, and from 2 to 3 days after surgery in the thermal hyperalgesia experiments.


CONCLUSIONS
Nuclear factor-kappa B decoy was conveyed and transduced into dorsal root ganglion both in vivo and in vitro. Additionally, nuclear factor-kappa B decoy reduced mechanical allodynia and thermal hyperalgesia in the rat inflammatory pain model, suggesting that inhibition of nuclear factor-kappa B with nuclear factor-kappa B decoy may represent a key mechanism for mediating inflammation or reducing inflammatory pain.
Inoue
Gen
G
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan. gen@rg7.so-net.ne.jp
Ochiai
Nobuyasu
N
Ohtori
Seiji
S
Nakagawa
Koichi
K
Gemba
Takefumi
T
Doya
Hideo
H
Ito
Toshinori
T
Koshi
Takana
T
Moriya
Hideshige
H
Takahashi
Kazuhisa
K
D000818:Animals; D004195:Disease Models, Animal; D006358:Hot Temperature / Q000009:adverse effects*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000008:administration & dosage*; D009841:Oligonucleotides / Q000008:administration & dosage; D010147:Pain Measurement; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology
D016328:NF-kappa B; D009841:Oligonucleotides