Constitutive activity of NF-κB-associated IKK enhances inflammatory pain sensitivity (2014)

Undergraduates: Olivia Eskew, Jane Hartung Sandra O'Buckley, Terrence Wong, Andrea Nackley

Faculty Advisor: Andrea Nackley
Department: Biology

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Constitutive activity of NF-κB-associated IKK enhances inflammatory pain sensitivity _x000D_
Objectives: We sought to understand if enhanced IKK activity increases inflammatory pain induced by complete Freund¿s adjuvant (CFA) at acute (1 h ¿ 1 d), subchronic (3 d - 7 d and chronic (9 d -13 d) post-injection time points. We hypothesized that mice with enhanced IKK activity (and thus, NF-κB signaling) would display heightened pain response to CFA as measured by mechanical and thermal pain sensitivity compared to mice with endogenous IKK activity. _x000D_
Methods: Mice received an intraplantar (i.pl.) injection of either CFA (20 L) or control incomplete Freund¿s adjuvant (IFA; 20 L). Following injection, mice were assessed for responses to punctate mechanical and thermal heat stimuli over a 13-day period. _x000D_
Results: IKK neg mice exhibited mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia only during the acute phase following CFA injection. In contrast, IKK ca mice exhibited mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia throughout the acute, subchronic and chronic phases following CFA injection. _x000D_
Conclusion: Here, we find that sustained elevations in IKK, a positive regulator of NF-κB, increase pain sensitivity in an animal model of inflammation. Future studies will explore the molecules downstream of IKK and NF-κB (e.g., catechol-O-methyltransferase (COMT)) that contribute to inflammatory pain._x000D_
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