A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity

Donghoon Kim, Ah Kim Myung, Ik Hyun Cho, Sun Kim Mi, Soojin Lee, Eun Kyeong Jo, Se Young Choi, Kyungpyo Park, Soo Kim Jong, Shizuo Akira, Sik Na Heung, Bae Oh Seog, Joong Lee Sung

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

The activation of spinal cord glial cells has been implicated in the development of neuropathic pain upon peripheral nerve injury. The molecular mechanisms underlying glial cell activation, however, have not been clearly elucidated. In this study, we found that damaged sensory neurons induce the expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, and inducible nitric-oxide synthase genes in spinal cord glial cells, which is implicated in the development of neuropathic pain. Studies using primary glial cells isolated from toll-like receptor 2 knock-out mice indicate that damaged sensory neurons activate glial cells via toll-like receptor 2. In addition, behavioral studies using toll-like receptor 2 knock-out mice demonstrate that the expression of toll-like receptor 2 is required for the induction of mechanical allodynia and thermal hyperalgesia due to spinal nerve axotomy. The nerve injury-induced spinal cord microglia and astrocyte activation is reduced in the toll-like receptor 2 knock-out mice. Similarly, the nerve injury-induced pro-inflammatory gene expression in the spinal cord is also reduced in the toll-like receptor 2 knock-out mice. These data demonstrate that toll-like receptor 2 contributes to the nerve injury-induced spinal cord glial cell activation and subsequent pain hypersensitivity.

Original languageEnglish
Pages (from-to)14975-14983
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number20
DOIs
Publication statusPublished - 2007 May 18

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity'. Together they form a unique fingerprint.

  • Cite this

    Kim, D., Myung, A. K., Cho, I. H., Mi, S. K., Lee, S., Jo, E. K., Choi, S. Y., Park, K., Jong, S. K., Akira, S., Heung, S. N., Seog, B. O., & Sung, J. L. (2007). A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. Journal of Biological Chemistry, 282(20), 14975-14983. https://doi.org/10.1074/jbc.M607277200