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

J Neurosci. 2008 Nov 26;28(48):12775-87. doi: 10.1523/JNEUROSCI.3512-08.2008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / immunology*
  • Hyperalgesia / immunology
  • Hyperalgesia / physiopathology
  • Injections, Spinal
  • Interleukin-18 / antagonists & inhibitors
  • Interleukin-18 / 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*
  • Peripheral Nervous System Diseases / physiopathology
  • Posterior Horn Cells / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-18 / antagonists & inhibitors
  • Receptors, Interleukin-18 / immunology
  • Signal Transduction / immunology
  • Spinal Cord / cytology
  • Spinal Cord / immunology*
  • Spinal Cord / physiopathology
  • Up-Regulation / immunology


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