Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB.

Abstract

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. 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. 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. 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.