T Sun1, W-G Song, Z-J Fu, Z-H Liu, Y-M Liu, S-L Yao. 1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: The activation of NF-kappaB pathway may contribute to neuropathic pain in CCIrats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.
Authors: Sandra M Garraway; Sarah A Woller; J Russell Huie; John J Hartman; Michelle A Hook; Rajesh C Miranda; Yung-Jen Huang; Adam R Ferguson; James W Grau Journal: Pain Date: 2014-08-29 Impact factor: 6.961
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