Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury.

Abstract

Interleukin (IL)-18 is an important regulator of innate and acquired immune responses. Here we show that both the IL-18 and IL-18 receptor (IL-18R), which are induced in spinal dorsal horn, are crucial for tactile allodynia after nerve injury. Nerve injury induced a striking increase in IL-18 and IL-18R expression in the dorsal horn, and IL-18 and IL-18R were upregulated in hyperactive microglia and astrocytes, respectively. The functional inhibition of IL-18 signaling pathways suppressed injury-induced tactile allodynia and decreased the phosphorylation of nuclear factor kappaB in spinal astrocytes and the induction of astroglial markers. Conversely, intrathecal injection of IL-18 induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Our results indicate that IL-18-mediated microglia/astrocyte interactions in the spinal cord have a substantial role in the generation of tactile allodynia. Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain.

• Authors: Kan Miyoshi, Koichi Obata, Takashi Kondo, Haruki Okamura, Koichi Noguchi
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 28 Issue 48 Pg. 12775-87 (Nov 26 2008) ISSN: 1529-2401 [Electronic] United States
• PMID: 19036970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-18
• NF-kappa B
• Receptors, Interleukin-18

Topics

• Animals
• Astrocytes (immunology)
• Hyperalgesia (immunology, physiopathology)
• Injections, Spinal
• Interleukin-18 (antagonists & inhibitors, immunology)
• MAP Kinase Signaling System (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (immunology)
• NF-kappa B (metabolism)
• Peripheral Nerve Injuries
• Peripheral Nerves (physiopathology)
• Peripheral Nervous System Diseases (immunology, physiopathology)
• Posterior Horn Cells (immunology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Interleukin-18 (antagonists & inhibitors, immunology)
• Signal Transduction (immunology)
• Spinal Cord (cytology, immunology, physiopathology)
• Up-Regulation (immunology)