4.3 Article

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

Journal

JOURNAL OF NEUROIMMUNOLOGY
Volume 283, Issue -, Pages 43-49

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2015.04.012

Keywords

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

Funding

  1. Pittsburgh Tissue Engineering Initiative
  2. NIH grant [P50-GM-53789]
  3. Duquesne University
  4. Duquesne University Chronic Pain Research Consortium
  5. Provost's Interdisciplinary Research Consortia Grant, Duquesne University

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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. (C) 2015 Elsevier B.V. All rights reserved.

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