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The Journal of Neuroscience, November 26, 2008, 28(48):12775-12787; doi:10.1523/JNEUROSCI.3512-08.2008

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Cellular/Molecular
Interleukin-18-Mediated Microglia/Astrocyte Interaction in the Spinal Cord Enhances Neuropathic Pain Processing after Nerve Injury

Kan Miyoshi,¹ Koichi Obata,¹ Takashi Kondo,¹ Haruki Okamura,² and Koichi Noguchi¹

¹Department of Anatomy and Neuroscience and ²Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan

Correspondence should be addressed to Dr. Koichi Noguchi, Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Email: noguchi{at}hyo-med.ac.jp

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 B 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.

Key words: microglia; astrocytes; neuropathic pain; IL-18; MAPK; NFB

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Received July 25, 2008; revised Oct. 3, 2008; accepted Oct. 9, 2008.

Correspondence should be addressed to Dr. Koichi Noguchi, Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Email: noguchi{at}hyo-med.ac.jp

This article has been cited by other articles:

				T. M. Cunha and Q. M. Dias Glial Modulation of Pain: A Step Beyond J. Neurosci., March 18, 2009; 29(11): 3340 - 3342. [Full Text] [PDF]

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