Intrathecal administration of cyclic AMP response element-binding protein-antisense oligonucleotide attenuates neuropathic pain after peripheral nerve injury and decreases the expression of N-Methyl-D-Aspartic receptors in mice

Gu,Xiaoping; Bo,Jinhua; Zhang,Wei; Sun,Xiaofeng; Zhang,Juan; Yang,Yan; Ma,Zhengliang

doi:10.3892/or.2013.2437

Intrathecal administration of cyclic AMP response element-binding protein-antisense oligonucleotide attenuates neuropathic pain after peripheral nerve injury and decreases the expression of N-Methyl-D-Aspartic receptors in mice

Authors:
- Xiaoping Gu
- Jinhua Bo
- Wei Zhang
- Xiaofeng Sun
- Juan Zhang
- Yan Yang
- Zhengliang Ma
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Affiliations: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Published online on: April 30, 2013 https://doi.org/10.3892/or.2013.2437
Pages: 391-398

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Abstract

The aim of the present study was to determine whether the cAMP response element binding protein (CREB) contributes to neuropathic pain during development stage. Adult (7-8 weeks old) male C57BL/6 mice weighing 20-25 g were used. Intrathecal catheter implantation and chronic constriction of the sciatic nerve of the animals were performed. Western blotting and reverse transcription PCR experiments were carried out. Our study demonstrated that the expression of spinal NMDAR after peripheral nerve injury was modulated by central CREB. Chronic constriction nerve injury (CCI) in mice induced thermal hyperalgesia and mechanical allodynia. The increase of NR1 and NR2B subunits of the NMDAR was significantly diminished by intrathecal administration of the CREB antisense oligonucleotide against CREB and pCREB. Additionally, nociceptive behavior induced by CCI was attenuated by intrathecal administration of the CREB antisense oligonucleotide during the period of injection, and the above effects of relieving pain lasted at least 12 days following the last injection. Our results suggested that central functional pCREB may contribute to the development of neuropathic pain and regulate the expression of the NR1 and NR2B subunits of the NMDAR in the process.

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