Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model.
Nuclear factor-kappa B (NF-kappaB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappaB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-kappaB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-kappaB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-kappaB decoy was transduced into DRGs in vivo. NF-kappaB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.
Suzuki
Munetaka
M
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Inoue
Gen
G
Gemba
Takefumi
T
Watanabe
Tomoko
T
Ito
Toshinori
T
Koshi
Takana
T
Yamauchi
Kazuyo
K
Yamashita
Masaomi
M
Orita
Sumihisa
S
Eguchi
Yawara
Y
Ochiai
Nobuyasu
N
Kishida
Shunji
S
Takaso
Masashi
M
Aoki
Yasuchika
Y
Takahashi
Kazuhisa
K
Ohtori
Seiji
S
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000819:agonists*; D011843:Radiculopathy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050436:Regulatory Elements, Transcriptional / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016207:Cytokines; D016328:NF-kappa B; D016650:Fluorescein-5-isothiocyanate; D015740:Calcitonin Gene-Related Peptide