title: In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282, USA; Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA. Electronic address: vasudevak@duq.edu.
authors.forename: Kiran
authors.initials: K
authors.lastname: Vasudeva
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: vodovotzy@upmc.edu.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: naa42@pitt.edu.
authors.forename: Nabil
authors.initials: N
authors.lastname: Azhar
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: barcdx2@upmc.edu.
authors.forename: Derek
authors.initials: D
authors.lastname: Barclay
authors.affiliation: Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA; Graduate School of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA. Electronic address: janjicj@duq.edu.
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Janjic
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282, USA; Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA. Electronic address: pollock@duq.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Pollock
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D059350:Chronic Pain / Q000276:immunology / Q000503:physiopathology*; D003198:Computer Simulation; D016207:Cytokines / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D058847:Inflammasomes / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology*; D008026:Ligation; D008297:Male; D008959:Models, Neurological; D009408:Nerve Compression Syndromes / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012585:Sciatica / Q000276:immunology / Q000503:physiopathology*; D049490:Systems Biology
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D020382:Interleukin-18
keywords: Chronic constriction injury; Dynamic bayesian network; IL-18; Neuroinflammation; Neuropathic pain