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Abstract

Objective: To investigate the relationship between NF-κB activity, cytokine levels, and pain sensitivities in a rodent model of osteoarthritis (OA). Method: OA was induced in transgenic NF-κB luciferase reporter mice via mono-iodoacetate (MIA) intra-articular injection. Using luminescent imaging we evaluated the temporal kinetics of NF-κB activity and its relationship to the development of pain sensitivities and serum cytokine levels in this model. Results: MIA induced a transient increase in joint-related NF-кB activity at early time points (day 3 post-injection) and an associated biphasic pain (mechanical allodynia) response. NF-кB activity, serum IL-6, IL-1β, and IL-10 accounted for ~75% of the variability in pain-related mechanical sensitivities in this model. Specifically, NF-кB activity was strongly correlated to mechanical allodynia and serum IL-6 levels in the inflammatory pain phase of this model (day 3), while serum IL-1β was strongly correlated to pain sensitivities in the chronic pain phase of the model (day 28). Conclusion: Our findings suggest that NF-кB activity, IL-6 and IL-1β may be playing distinct roles in pain sensitivity development in this model of arthritis and may act to distinguish the acute from chronic pain phases of this model. This work establishes luminescent imaging of NF-кB activity as a novel imaging biomarker of pain sensitivities in this model of OA.