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Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat

Gene Therapy volume 12, pages 59–66 (2005)Cite this article

Abstract

N-methyl-D-aspartate (NMDA) receptor activation, at the level of the spinal cord, has been shown to play an important role in the facilitation of nociception in several animal models. However, the use of NMDA antagonists as analgesics is limited by serious side effects due to nonselective effects among the NMDA receptor subtypes. Recent discoveries revealed that the transfection of small interfering RNAs (siRNAs) into animal cells resulted in the potent, long-lasting, post-transcriptional silencing of specific genes. Thus, we investigated the effect of intrathecal (i.t.) injection of siRNAs targeting NMDA-R2B receptor subunit protein (NR2B) receptors, a subunit of NMDA receptor, for the modulation of pain. The results indicate that the use of siRNA targeting the NR2B subunit not only decreased the expression of NR2B mRNA and its associated protein, as demonstrated by real-time PCR and Western blotting, but also abolished formalin-induced pain behaviors in rat model. The peak effect occurred on day 3 for mRNA and day 7 for its protein, following i.t. injection of 5 μg of siRNA-NR2B. These data prove the feasibility of i.t. siRNAs in the investigation of functional gene expression in the context of whole animal behavior for the management of chronic pain.

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Acknowledgements

This work was supported in parts by the University Integration Program from the Ministry of Education and by National Science Council Grant NSC 92-2314-B-182A-141.

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Authors and Affiliations

  1. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC

    P-H Tan & J-T Cheng

  2. Department of Anesthesiology, E-DA Hospital, I-Shou Universit, Kaohsiung, Taiwan, ROC

    P-H Tan & L-C Yang

  3. Department of Anesthesiology, Cha-Yi Christian Hospital, Taiwan, ROC

    H-C Shih

  4. Deaprtment of Obstetrics and Gynecology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, ROC

    K-C Lan

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Tan, PH., Yang, LC., Shih, HC. et al. Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat. Gene Ther 12, 59–66 (2005). https://doi.org/10.1038/sj.gt.3302376

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