TNF and rheumatoid arthritis: To establish a suitable proinflammatory phenotype for our cultures, we used primary FLS derived from mice undergoing acute, unilateral complete Freund's adjuvant (CFA)-induced knee inflammation, which can produce neuronal hyperexcitability.13 We also tested primary mouse knee-derived FLS treated with TNF-α, one of the main cytokines upregulated in CFA-injected mouse tissues65 and in inflammatory arthritis,53 and validated our results in FLS derived from human OA and RA patients.