In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain

J Neuroimmunol. 2015 Jun 15:283:43-9. doi: 10.1016/j.jneuroim.2015.04.012. Epub 2015 Apr 28.


Inflammation is associated with peripheral neuropathy, however the interplay among cytokines, chemokines, and neurons is still unclear. We hypothesized that this neuroinflammatory interaction can be defined by computational modeling based on the dynamics of protein expression in the sciatic nerve of rats subjected to chronic constriction injury. Using Dynamic Bayesian Network inference, we identified interleukin (IL)-18 as a central node associated with neuropathic pain in this animal model. Immunofluorescence supported a role for inflammasome activation and induction of IL-18 at the site of injury. Combined in vivo and in silico approaches may thus highlight novel targets in peripheral neuropathy.

Keywords: Chronic constriction injury; Dynamic bayesian network; IL-18; Neuroinflammation; Neuropathic pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Chronic Pain / immunology
  • Chronic Pain / physiopathology*
  • Computer Simulation*
  • Cytokines / physiology
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology
  • Inflammasomes / physiology
  • Inflammation Mediators / physiology
  • Interleukin-18 / physiology*
  • Ligation
  • Male
  • Models, Neurological*
  • Nerve Compression Syndromes / immunology
  • Nerve Compression Syndromes / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / immunology
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiopathology
  • Sciatica / immunology
  • Sciatica / physiopathology*
  • Systems Biology


  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • Interleukin-18