As for longer-term cold application on arthritic joints, the optimal protocol could be twice a day for 14 consecutive days, which showed beneficial effects on pain and disease activity in RA patients [1], This subchronic application protocol, when applied in the murine model of adjuvant-induced arthritis, also significantly improved arthritis score, joint swelling, and local and systemic IL-6 and VEGF levels—both at the gene and protein levels. The gene discussed is IL6; the disease is rheumatoid arthritis.