NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.
Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.
Sakaue
G
G
Department of Anesthesiology, Osaka University Medical School, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.
Shimaoka
M
M
Fukuoka
T
T
Hiroi
T
T
Inoue
T
T
Hashimoto
N
N
Sakaguchi
T
T
Sawa
Y
Y
Morishita
R
R
Kiyono
H
H
Noguchi
K
K
Mashimo
T
T
D000818:Animals; D015815:Cell Adhesion Molecules; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat