Efeito da microinjeção de migalina na substância cinzenta periaquedutal dorsomedial na dor neuropática crônica e ansiedade em ratos com diabetes induzido por estreptozotocina

Abstract

Diabetes mellitus (DM) is one of the main diseases that affect the entire world and approximately more than 463 million people suffer from this disease. DM presents alterations in the pancreas that cause deficiency in insulin production, generating two types of DM, type 1 or insulin-dependent and type 2 or non-insulin dependent. Thus, type 1 DM can develop complications such as nerve damage and micro/macrovascular alterations known as diabetic neuropathy (DN). DN can develop comorbidities such as anxiety, depression or sleep disturbance. The present study aimed to evaluate the effect of microinjection of the synthetic polyamine Migalin in the dorsomedial periaqueductal gray matter (PAGdm) on chronic neuropathic pain and anxiety in Wistar rats with streptozotocin-induced DM (STZ). Type 1 DM was induced in rats with intraperitoneal STZ, with a single dose of 60 mg/kg, after that, the animals' weight and blood glucose were monitored, in addition to their development of DN, applying mechanical allodynia tests with von frey and cold with the acetone test. At 28 days of DM induction, microinjection of mygalin (0.002 μg/μL, 0.02 μg/μL and 0.2 μg/μL) in the PAGdm was performed. Elevated plus maze (EPM) and open field tests were evaluated. Thus, animals treated with STZ showed increased glycemia from 48h after induction and remaining during the study period. Weight loss was observed on day 7 and continued until day 28. Animals treated with STZ showed greater aversive responses than the control group with the von Frey's innocuous test, and when treated with migalin (0, 002 μg/μL, 0.02 μg/μL and 0.2 μg/μL) the response decreased at times 15, 30 and 45 minutes, and the highest dose 0.2 μg/μL was prolonged up to 90 minutes. In the acetone test, the neuropathic groups showed altered responses, however, when the treated groups were administered with migaline, it showed improvement at times 5, 15 and 30 minutes and only the highest dose 0.2 μg/μL reached 45 minutes. The open field test and EPM did not show significant differences between groups and the administration of mygalin at the three different doses had no impact on behavior. The results suggest that mygalin applied to PAGdm has analgesic potential and may be useful in the treatment of DN, but does not interfere with the animals' behavior.