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

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-alpha, interleukin-1beta, 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.

• Authors: Donghoon Kim, Myung Ah Kim, Ik-Hyun Cho, Mi Sun Kim, Soojin Lee, Eun-Kyeong Jo, Se-Young Choi, Kyungpyo Park, Joong Soo Kim, Shizuo Akira, Heung Sik Na, Seog Bae Oh, Sung Joong Lee
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 20 Pg. 14975-83 (May 18 2007) ISSN: 0021-9258 [Print] United States
• PMID: 17355971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Animals
• Astrocytes (metabolism, pathology)
• Cells, Cultured
• Cytokines (metabolism)
• Gene Expression Regulation (genetics)
• Hyperalgesia (genetics, metabolism)
• Inflammation (genetics, metabolism, pathology)
• Mice
• Mice, Knockout
• Nitric Oxide Synthase Type II (metabolism)
• Pain (genetics, metabolism, pathology)
• Peripheral Nerve Injuries
• Peripheral Nerves (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (metabolism, pathology)
• Toll-Like Receptor 2 (deficiency, metabolism)