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

•Multiplex cytokine protein expression in rat CCI sciatic nerve was studied.•Immunohistology of the CCI sciatic nerve confirms inflammasome activation.•Dynamic Bayesian Network inference identified interleukin (IL)-18 as a central node.•DBN shows interactions among IFN-γ, IL-1β and IL-18 contribute to neuropathic pain.•In vivo/in silico approach provides unique insight into chronic neuropathic pain.

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.

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