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...

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Bibliographic Details
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
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Summary: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.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2015.04.012