Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB.
BACKGROUND
Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-kappaB antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal hyperalgesia in a chronic constriction injury (CCI) model of rats.


METHODS
Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI model was established. Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF-kappaB were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-kappaB p65 expression was assessed by western blot.


RESULTS
CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-kappaB p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.


CONCLUSIONS
The activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.
Sun
T
T
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Song
W-G
WG
Fu
Z-J
ZJ
Liu
Z-H
ZH
Liu
Y-M
YM
Yao
S-L
SL
D000818:Animals; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy; D007278:Injections, Spinal; D008297:Male; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D059408:Pain Management; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics* / Q000502:physiology
D016376:Oligonucleotides, Antisense; D051996:Transcription Factor RelA