Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury.
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.
Miyoshi
Kan
K
Department of Anatomy and Neuroscience, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Obata
Koichi
K
Kondo
Takashi
T
Okamura
Haruki
H
Noguchi
Koichi
K
D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D006930:Hyperalgesia / Q000276:immunology / Q000503:physiopathology; D007278:Injections, Spinal; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053724:Receptors, Interleukin-18 / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology* / Q000503:physiopathology; D015854:Up-Regulation / Q000276:immunology
D020382:Interleukin-18; D016328:NF-kappa B; D053724:Receptors, Interleukin-18