Hyperalgesic effects of γ-aminobutyric acid transporter I in mice

Jia Hua Hu, Na Yang, Ying Hua Ma, Xiao Gang Zhou, Jie Jiang, Shu Hui Duan, Zhen Tong Mei, Jian Fei, Li He Guo

Research output: Contribution to journalArticle

Abstract

The present study focused on the involvement of γ-aminobutyric acid transporter I (GAT1) in pain. We found that GABA uptake was increased in mouse spinal cord at 20 min and 120 min after formalin injection and in mouse brain at 120 min, but not 20 min, after formalin injection. In addition, the antinociceptive effects of GAT1-selective inhibitors were examined using assays of thermal (tail-flick) and chemical (formalin and acetic acid) nociception in C57BL/6J mice. The GAT1-selective inhibitors, ethyl nipecotate and NO-711, exhibited significant antinociceptive effects in these nociceptive assays. To study further the effects of GAT1 on pain, we used two kinds of GAT1-overexpressing transgenic mice (under the control of a CMV promoter or a NSE promoter) to examine the nociceptive responses in these mice. In the thermal, formalin, and acetic acid assays, both kinds of transgenic mice displayed significant hyperalgesia after nociceptive stimuli. In addition, the μ opioid receptor antagonist naloxone had no influence on nociceptive responses in wild-type and transgenic mice. The results indicate that GAT1 is involved in the regulation of pain processes, and point to the possibility of developing analgesic drugs that target GAT1 other than opioid receptors.

Original languageEnglish (US)
Pages (from-to)565-572
Number of pages8
JournalJournal of neuroscience research
Volume73
Issue number4
DOIs
StatePublished - Aug 15 2003

Keywords

  • Antinociception
  • GABA transporter
  • GABA uptake
  • Overexpressing
  • Pain

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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  • Cite this

    Hu, J. H., Yang, N., Ma, Y. H., Zhou, X. G., Jiang, J., Duan, S. H., Mei, Z. T., Fei, J., & Guo, L. H. (2003). Hyperalgesic effects of γ-aminobutyric acid transporter I in mice. Journal of neuroscience research, 73(4), 565-572. https://doi.org/10.1002/jnr.10677