1). However, a slight increase in SCV was observed in diabetic mice (n = 13). The SCV in diabetic mice was significantly lower than that in healthy mice from 1 to 9 weeks after STZ injection. There was no significant difference in the amplitude of SNAPs between groups during the experimental period (data not shown). FK866 Figure 1 Sensory nerve conduction velocity of tail nerves in healthy and diabetic mice. Diabetic mice (DM) (filled circles) (n = 13), healthy mice Inhibitors,research,lifescience,medical (control) (open circles) (n = 7). DM versus control: *P < 0.05, **P < 0.01, ***P < 0.001, ... Nociceptive threshold of diabetic and healthy ddY mice The nociceptive threshold of the hindpaw was measured at 1, 3, 5, 7, and

9 weeks after STZ injection in diabetic and healthy Inhibitors,research,lifescience,medical ddY mice by the paw-pressure test.

The mean nociceptive threshold in diabetic mice (n = 13) was higher than that in healthy mice (n = 7) throughout the experimental period (Fig. 2). There was a significant difference in the nociceptive threshold between healthy and diabetic mice at 5, 7, and 9 weeks after STZ injection. Figure 2 Nociceptive threshold of the hindpaw in healthy and diabetic mice. Diabetic mice (DM) (filled circles) (n = 13), healthy ddY mice (control) (open circles) (n = 7). DM versus control: *P < 0.05, **P < 0.01, unpaired Student's t-test. The correlation between SCV and the nociceptive Inhibitors,research,lifescience,medical threshold was examined in diabetic Inhibitors,research,lifescience,medical and healthy mice. We found a significant negative correlation between SCV and the nociceptive threshold (n = 114, r = −0.516, P < 0.001) (Fig. 3). Figure 3 Correlation between sensory conduction velocity (SCV) of the tail nerve and the nociceptive threshold of the hindpaw in healthy and diabetic mice; n = 114, r = −0.516, P < 0.001, Pearson's correlation coefficient

test. SCV and nociceptive threshold of insulin-treated diabetic mice Two days after STZ injection, diabetic mice were implanted with insulin pellets (n = 8), which remained in place for 7 weeks. Sensory nerve conduction studies of tail nerves and paw-pressure tests were performed Inhibitors,research,lifescience,medical at 0, 2, 4, and 7 weeks after STZ injection. We also examined untreated diabetic mice (n = 8) and healthy ddY mice (n = 8) as control groups. Insulin treatment improved SCV in diabetic mice at until 2 and 4 weeks after STZ injection (Fig. 4A), and prevented the elevation of the nociceptive threshold (hypoalgesia) in diabetic mice at 2 and 4 weeks (Fig. 4B). At 7 weeks after STZ injection, blood glucose level was elevated in treated diabetic mice (Fig. 4C), and the preventive effects of the insulin pellets were diminished (Fig. 4A and B). Figure 4 Insulin treatment increased sensory conduction velocity (SCV) of the tail nerve (A) and prevented the elevation of the nociceptive threshold (B) in diabetic mice. Blood glucose levels (C) and body weight (D) were measured at the indicated time points. …