Figure 6.

The effect of BT44 in rats with diabetes mellitus. Schemes of the STZ experiments are shown in panel (a). STZ was injected on day −1. The black vertical lines indicate the days when behavioral tests were performed. Rats received BT44 or vehicle subcutaneously once daily every other day for two or six weeks starting the day after the injection of STZ (day 0). Behavioral tests were performed before the injection of STZ (BL), before the first BT44 injection (day 0) and on weeks 1, 2, 3, 4, and 6. BT44 alleviates the mechanical hyperalgesia (b) and the cold allodynia (c and d) in the STZ-treated animals. In (b), thresholds (g) to mechanical stimulation are shown. Panel (c) shows cold allodynia responses to acetone (positive responses/five trials), and panel (d) shows the area under curve of the normalized values of d0–d14 in the acetone test for each group. Data represent mean ± SEM. In (b), **P < 0.01, ****P < 0.0001 (two-way ANOVA with Dunnett’s multiple comparisons test; reference: the corresponding vehicle-group without BT44 treatment). In (d), *P < 0.05, **** P < 0.0001 (Krustal–Wallis test with Dunn’s multiple comparison test). n = 8–19. BL: baseline; VEH: vehicle; d: days; HC: healthy control; DM: diabetes mellitus; AUC: area under curve.