Fig. 1

Schematic experimental procedure of two arthritic pain models. On the day before CFA injection (day 0), basal behavioral tests and joint diameters were detected. Then, mice were injected with CFA in hind metatarsal footpad (upper paradigm) or into intra-articular space of knee (lower paradigm) to induce arthritic pain of ankle and knee respectively. For the knee arthritis model, the mice received another three intra-articular CFA injection on day 7, 14, 21. For the control mice, the same volume of saline was injected at the same time points with that of CFA injection. Behavioral tests were performed on day 3, 7, 14 16, 18 for ankle arthritic pain model and day 4, 11, 17, 24, 26, 28 for knee arthritic pain model. NB001 (3 mg/kg, i.p.) or saline was injected to mice once daily from day 14 to day 18 in ankle arthritis model and day 24 to day 28 in knee arthritis model. At the first day of treatment (day 14 and day 24 respectively), NB001 or saline was administrated after the behavioral tests. On day 15, 17 in ankle arthritis model and day 25, 27 in knee arthritis model, the mice were just received NB001 or saline administration and no behavioral tests were performed. The related behavioral tests were conducted within 2.5 h on day 16, 18 and day 26, 28 in two models respectively following NB001 or saline treatment