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BJA Advance Access published online on August 1, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael209
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted May 19, 2006

Laboratory Investigation

Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-{kappa}B

T. Sun 1, W.-G. Song 1, Z.-J. Fu 2, Z.-H. Liu 3, Y.-M. Liu 4, and S.-L. Yao 4 *

1 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Pain Management, Shandong Provincial Hospital, Jinan 250021, China
2 Department of Pain Management, Shandong Provincial Hospital, Jinan 250021, China
3 Department of Anesthesiology, The Second Hospital in Shenzhen, Shenzhen 518035, China
4 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

* To whom correspondence should be addressed.
S.-L. Yao, E-mail: yaoshanglong{at}eyou.com


  Abstract

Background. Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-{kappa}B 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-{kappa}B were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-{kappa}B p65 expression was assessed by western blot.

Results. CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-{kappa}B p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-{kappa}B p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.

Conclusion. The activation of NF-{kappa}B pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-{kappa}B could be a potential new strategy for the treatment of neuropathic pain.

Keywords: antisense oligodeoxynucleotides; complications, chronic constriction injury; NF-{kappa}B; spinal cord.
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