Objective: 

Previous experimental data indicate that ATP-sensitive potassium channel openers have promising effects on experimental diabetic neuropathy. We have investigated the possible effects of levosimendan, a calcium sanitizer agent with prominent K(ATP) channel opening activity, on painful diabetic neuropathy in a mice model.

Methods: 

Diabetes was induced in adult male Balb/C mice by injection of streptozotocin [200 mg/kg intraperitoneally (i.p.)] and 4 weeks after induction of diabetes (serum glucose >=300 mg/dL) plantar test was performed and paw withdrawal latency was considered as pain threshold. Levosimendan (1 and 2 mg/kg body weight) was administered i.p. and plantar tests were repeated. Data were analyzed by Kruskal–Wallis one-way analysis of variance (ANOVA) followed by a pairwise comparison using a Dunnett's t-test on the ranked data.

Results: 

The vehicle for levosimendan had no significant effect on pain threshold. Levosimendan (1, 2 mg/kg) significantly reduced the pain threshold values of diabetic mice. The effect was time dependent, and at about the same extent for the both doses tested. Normalized pain threshold values were reduced from 1 to 0.78 (P<0.001, n=8), 0.77 (P<0.001, n=8) and 0.77 (P<0.001, n=8) 10, 20 and 30 minutes after administration of 1 mg/kg levosimendan, respectively.

Conclusions: 

Results obtained from this in vivo behavioral test indicate that levosimendan has promising therapeutic potential for the treatment of diabetic neuropathic pain.