Investigation of antihyperalgesic effects of different doses of sildenafil and metformin in alloxan-induced diabetic neuropathy in mice

Neuropathy is one of the most frequent and continuously growing complications of diabetes. Due to the multitude of mechanisms involved in the pathogenesis of diabetic neuropathy and the fact that current therapeutic strategies have limited success in relieving pain, the aim of our study was to investigate the antihyperalgesic action of two possible effective therapeutic agents: sildenafil (a phosphodiesterase 5 inhibitor) and metformin (an antihyperglycemic). Three consecutive doses of 150 mg/kg bw of alloxan were used to induce diabetic neuropathy. Metformin showed an antihyperalgesic effect for all 3 tested doses (150 mg/kg bw, 250 mg/kg bw and 500 mg/kg bw), while for sildenafil, only doses of 2.5 mg/kg bw and 3 mg/kg bw demonstrated a significant increase in pain reaction latency after 14 days of treatment in the hot-plate test. On the other hand, metformin 150 mg/kg bw, metformin 500 mg/kg bw, sildenafil 1.5 mg/kg bw and sildenafil 3 mg/kg bw showed the best antihyperlagesic effect in the tail withdrawal test after 14 days of treatment. Blood count highlighted increased WBC (white blood cells) values and decreased RBC (red blood cells), Hb (haemoglobin), and Hct (haematocrit) values in all diabetic groups, except the metformin 250 mg/kg bw and metformin 500 mg/kg bw groups, which showed the best glycaemic control according to blood fructosamine values. These findings indicate that alterations in blood count parameters may be prevented by good glycemic control. MPV (mean platelet volume) values were statistically increased for all diabetic groups when compared to the non-diabetic control group. Further studies are needed to investigate the mechanisms of action involved in antihyperalgesic activity.