The Influence of Long-term Diabetes Mellitus on Pain Response in Mice: In Vivo Models of Painful Diabetic Neuropathy (PDN)

Abstract

ABSTRACT

Painful diabetic neuropathy (PDN) is a complication of long-term Diabetes Mellitus (DM) characterized by hyperalgesia and allodynia. In streptozotocin (STZ)-induced diabetic mice, higher dose of STZ and lengthen hiperglycemic condition results in better model of PDN. However, higher dose of STZ tend to induce mortality. Evaluate the doses of STZ that caused PDN with less mortality rate and the timing of pain behavior development in mice model of PDN. Balb/c mice were divided into non-diabetic and STZ-induced diabetic group. The doses of STZ were started from 180 mg/kg i.p. Serum glucose levels were measured 7 days after induction. Mice with glucose levels ≥ 200 mg/dl were considered as diabetic. Pain behaviour was determined by four method i.e. hot plate, tail flick test, von Frey fillament and Randall Selitto,measured on week-0 (baseline), 1, 2, 3, 4 and 5. Data were presented as mean±SEM. The mean differences between weeks were evaluated by One-Way ANOVA and the mean differences between two groups by independent t-test. STZ doses 180 mg/kg, 150 mg/kg and 120 mg/kg caused 100% death and STZ 90 mg/kg failed to induce diabetic condition. STZ 110 mg/kg resulted in 0% mortality while it induced diabetes in 100% mice. Latency time toward thermal stimulus decreased to 5.8 s at 1^st week after the mice become diabetes  (p<0.05) and it was continued decrease until 4^th week. The same result was also showed in tail flick test and Randal Selitto. The pain sensitivity determined by von Frey filament decreased to 1.37 g at week 1 (p<0.05) and continued decrease until 5^th week. Optimum dose of STZ to induce PDN was 110 mg/kg. Pain behaviour of diabetic group was observed at 1^st week after diabetic and continued until 4^th week.

Keywords: PDN, hot plate, tail flick test, von Frey fillament, Randall Selitto