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

• Published in: Journal of neuroimmunology 2015-06, Vol.283, p.43-49
• Main Authors: Vasudeva, Kiran, Vodovotz, Yoram, Azhar, Nabil, Barclay, Derek, Janjic, Jelena M, Pollock, John A
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Bayes Theorem; Chronic constriction injury; Chronic Pain - immunology; Chronic Pain - physiopathology; Computer Simulation; Cytokines - physiology; Dynamic bayesian network; Hyperalgesia - etiology; Hyperalgesia - physiopathology; IL-18; Inflammasomes - physiology; Inflammation Mediators - physiology; Interleukin-18 - physiology; Ligation; Male; Models, Neurological; Nerve Compression Syndromes - immunology; Nerve Compression Syndromes - physiopathology; Neuroinflammation; Neurology; Neuropathic pain; Rats; Rats, Sprague-Dawley; Sciatic Nerve - immunology; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; Sciatica - immunology; Sciatica - physiopathology; Systems Biology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2015.04.012

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.