Fig 2: Activation of RAGE by S100B accelerates the onset of anxiety in CFA-treated mice. a, Schematic diagram showing where and when S100B, S100B+FPS-ZM1 or vehicle was injected into CFA-treated mice. b, Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of CFA-treated mice after S100B, S100B+FPS-ZM1 or vehicle injection. c, Heatmap of CFA-treated mice in the elevated plus maze after S100B, S100B+FPS-ZM1 or vehicle injection (the cross arm of the map is the closed arm, and the longitudinal arm is the open arm). d, Calculation of the percentage of time spent in the open arm (RTOA) and the percentage of distance traveled in the open arm (DOA) by the mice in the elevated plus maze. e, Heatmap of CFA-treated mice in the open field test after S100B, S100B+FPS-ZM1 or vehicle injection. f, Calculation of the percentage of mouse retention time in the central area (RTCA) and the percentage of mouse distance traveled in the central area (DCA) in the open field test. ** p < 0.01. ns: not significant

Fig 3: S100B was upregulated at 9d after CFA treatment, and intra-ACC injection of S100B activated RAGE but did not induce pain-related behavioral changes under normal conditions. a, Immunofluorescence of S100B in ACC astrocytes at different stages after intraplantar CFA or saline injection (scale bar = 50 μm). b, Count numbers of S100B-positive cells. c, Expression level of S100B in the ACC at different stages after intraplantar CFA or saline injection, as measured by ELISA. d, Schematic diagram showing where and when S100B or vehicle was injected into saline-treated mice. e, Immunofluorescence of RAGE in the ACC after intra-ACC injection of S100B or vehicle (scale bar = 50 μm). f, Count numbers of RAGE-positive cells. g, Expression level of RAGE in the ACC after intra-ACC injection of S100B or vehicle, as measured by ELISA. h, Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of saline-treated mice after S100B or vehicle injection. i, Heatmap of saline-treated mice in the elevated plus maze after S100B or vehicle injection (the cross arm of the map is the closed arm, and the longitudinal arm is the open arm). j, Calculation of the percentage of time spent in the open arm (RTOA) and the percentage of distance traveled in the open arm (DOA) by the mice in the elevated plus maze. k, Heatmap of saline-treated mice in the open field test after S100B or vehicle injection. l, Calculation of the percentage of mouse retention time in the central area (RTCA) and the percentage of mouse distance traveled in the central area (DCA) in the open field test.** p < 0.01. ns: not significant